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1.  4-1BB–enhanced expansion of CD8+ TIL from triple-negative breast cancer unveils mutation-specific CD8+ T cells 
Cancer immunology research  2017;5(6):439-445.
Triple negative breast cancer (TNBC) highly infiltrated with CD8+ tumor-infiltrating lymphocytes (TILs) has been associated with improved prognosis. This observation led us to hypothesize that CD8+ TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8+ TILs in solid cancers other than melanoma. To overcome this obstacle, we used an agonistic antibody (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8+ T cells. This approach was first utilized in melanoma and, in this study, led to advantageous growth of TILs for the majority of TNBC tumors tested. The agonistic antibody was only added in the initial setting of the culture and yet favored the propagation of CD8+ TILs from TNBC tumors. These expanded CD8+ TILs were capable of cytotoxic functions and were successfully utilized to demonstrate the presence of immunogenic mutations in autologous TNBC tumor tissue without recognition of the wild-type counterpart. Our findings open the way for a successful adoptive immunotherapy for TNBC.
doi:10.1158/2326-6066.CIR-16-0364
PMCID: PMC5525328  PMID: 28473315
TIL; Triple negative breast cancer; 4-1BB/CD137; mutated peptide
2.  Validation of multiplex immunofluorescence panels using multispectral microscopy for immune-profiling of formalin-fixed and paraffin-embedded human tumor tissues 
Scientific Reports  2017;7:13380.
Immune-profiling is becoming an important tool to identify predictive markers for the response to immunotherapy. Our goal was to validate multiplex immunofluorescence (mIF) panels to apply to formalin-fixed and paraffin-embedded tissues using a set of immune marker antibodies, with the Opal™ 7 color Kit (PerkinElmer) in the same tissue section. We validated and we described two panels aiming to characterize the expression of PD-L1, PD-1, and subsets of tumor associated immune cells. Panel 1 included pancytokeratin (AE1/AE3), PD-L1, CD4, CD8, CD3, CD68, and DAPI, and Panel 2 included pancytokeratin, PD-1, CD45RO, granzyme B, CD57, FOXP3, and DAPI. After all primary antibodies were tested in positive and negative controls by immunohistochemistry and uniplex IF, panels were developed and simultaneous marker expressions were quantified using the Vectra 3.0™ multispectral microscopy and image analysis InForm™ 2.2.1 software (PerkinElmer).These two mIF panels demonstrated specific co-localization in different cells that can identify the expression of PD-L1 in malignant cells and macrophages, and different T-cell subpopulations. This mIF methodology can be an invaluable tool for tumor tissue immune-profiling to allow multiple targets in the same tissue section and we provide that is accurate and reproducible method when is performed carefully under pathologist supervision.
doi:10.1038/s41598-017-13942-8
PMCID: PMC5645415  PMID: 29042640
3.  Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy 
Cell  2016;167(2):397-404.e9.
SUMMARY
Antibody blockade of the inhibitory CTLA-4 pathway has led to clinical benefit in a subset of patients with metastatic melanoma. Anti-CTLA-4 enhances T cell responses, including production of IFN-γ, which is a critical cytokine for host immune responses. However, the role of IFN-γ signaling in tumor cells in the setting of anti-CTLA-4 therapy remains unknown. Here we demonstrate that patients identified as non-responders to anti-CTLA-4 (ipilimumab) have tumors with genomic defects in IFN-γ pathway genes. Furthermore, mice bearing melanoma tumors with knockdown of IFN-γ receptor 1 (IFNGR1) have impaired tumor rejection upon anti-CTLA-4 therapy. These data highlight that loss of the IFN-γ signaling pathway is associated with primary resistance to anti-CTLA-4 therapy. Our findings demonstrate the importance of tumor genomic data, especially IFN-γ related genes, as prognostic information for patients selected to receive treatment with immune checkpoint therapy.
eTOC
Genomic defects in the interferon pathway genes reduce the chance of response to immune checkpoint blockade therapy with anti-CTLA-4 for melanoma in humans and experimental models.
doi:10.1016/j.cell.2016.08.069
PMCID: PMC5088716  PMID: 27667683
melanoma; anti-CTLA-4; ipilimumab; IFN-γ signaling; copy number alteration; primary resistance
4.  Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma 
NPJ genomic medicine  2017;2:10.
Appreciation for genomic and immune heterogeneity in cancer has grown though the relationship of these factors to treatment response has not been thoroughly elucidated. To better understand this, we studied a large cohort of melanoma patients treated with targeted therapy or immune checkpoint blockade (n = 60). Heterogeneity in therapeutic responses via radiologic assessment was observed in the majority of patients. Synchronous melanoma metastases were analyzed via deep genomic and immune profiling, and revealed substantial genomic and immune heterogeneity in all patients studied, with considerable diversity in T cell frequency, and few shared T cell clones (<8% on average) across the cohort. Variables related to treatment response were identified via these approaches and through novel radiomic assessment. These data yield insight into differential therapeutic responses to targeted therapy and immune checkpoint blockade in melanoma, and have key translational implications in the age of precision medicine.
doi:10.1038/s41525-017-0013-8
PMCID: PMC5557036
5.  Absence of Grail promotes CD8+ T cell anti-tumour activity 
Nature Communications  2017;8:239.
T-cell tolerance is a major obstacle to successful cancer immunotherapy; thus, developing strategies to break immune tolerance is a high priority. Here we show that expression of the E3 ubiquitin ligase Grail is upregulated in CD8+ T cells that have infiltrated into transplanted lymphoma tumours, and Grail deficiency confers long-term tumour control. Importantly, therapeutic transfer of Grail-deficient CD8+ T cells is sufficient to repress established tumours. Mechanistically, loss of Grail enhances anti-tumour reactivity and functionality of CD8+ T cells. In addition, Grail-deficient CD8+ T cells have increased IL-21 receptor (IL-21R) expression and hyperresponsiveness to IL-21 signalling as Grail promotes IL-21R ubiquitination and degradation. Moreover, CD8+ T cells isolated from lymphoma patients express higher levels of Grail and lower levels of IL-21R, compared with CD8+ T cells from normal donors. Our data demonstrate that Grail is a crucial factor controlling CD8+ T-cell function and is a potential target to improve cytotoxic T-cell activity.
Grail is an E3 ubiquitin ligase that inhibits T-cell receptor signalling in CD4+ T cells. Here the authors show Grail also limits IL-21 receptor expression and function in CD8+ T cells, is overactive in these cells in patients with lymphoma, and promotes tumour development in a lymphoma transplant mouse model.
doi:10.1038/s41467-017-00252-w
PMCID: PMC5552797  PMID: 28798332
6.  Parallel profiling of immune infiltrate subsets in uveal melanoma versus cutaneous melanoma unveils similarities and differences: A pilot study 
Oncoimmunology  2017;6(6):e1321187.
ABSTRACT
The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8+ T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases. Tumors from metastatic UM patients showed a lower success rate of tumor-infiltrating lymphocyte (TIL) growth compared with metastatic CM (45% vs. 64% success), with a significantly lower quantity of UM TIL expanded overall. These studies suggest that UM and CM are immunologically distinct, and provide potential explanation for the impaired success of immunotherapy in UM.
doi:10.1080/2162402X.2017.1321187
PMCID: PMC5486182
Cutaneous melanoma; immune profile; tumor infiltrating lymphocytes; uveal melanoma
8.  A Novel Method to Generate and Expand Clinical-Grade, Genetically Modified, Tumor-Infiltrating Lymphocytes 
Following the clinical success achieved with the first generation of adoptive cell therapy (ACT) utilizing in vitro expanded tumor-infiltrating lymphocytes (TILs), the second and third generations of TIL ACT are evolving toward the use of genetically modified TIL. TIL therapy generally involves the transfer of a high number of TIL, ranging from 109 to 1011 cells. One of the technical difficulties in genetically modifying TIL, using a retroviral vector, is the ability to achieve large expansion of transduced TIL, while keeping the technique suitable to a Good Manufacturing Practices (GMP) environment. Consequently, we developed and optimized a novel method for the efficient production of large numbers of GMP-grade, gene-modified TIL for the treatment of patients with ACT. The chemokine receptor CXCR2 was used as the gene of interest for methodology development. The optimized procedure is currently used in the production of gene-modified TIL for two clinical trials for the treatment of metastatic melanoma at MD Anderson Cancer Center.
doi:10.3389/fimmu.2017.00908
PMCID: PMC5539190
tumor-infiltrating lymphocytes; retroviral-transduction; adoptive cell therapy; genetic modification; Good Manufacturing Practice; clinical-grade
9.  31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): late breaking abstracts 
Althammer, Sonja | Steele, Keith | Rebelatto, Marlon | Tan, Tze Heng | Wiestler, Tobias | Schmidt, Guenter | Higgs, Brandon | Li, Xia | Shi, Li | Jin, Xiaoping | Antal, Joyce | Gupta, Ashok | Ranade, Koustubh | Binning, Gerd | Bellmunt, Joaquim | de Wit, Ronald | Vaughn, David J. | Fradet, Yves | Lee, Jae Lyun | Fong, Lawrence | Vogelzang, Nicholas J. | Climent, Miguel A. | Petrylak, Daniel P. | Choueiri, Toni K. | Necchi, Andrea | Gerritsen, Winald | Gurney, Howard | Quinn, David I. | Culine, Stéphane | Sternberg, Cora N. | Mai, Yabing | Puhlmann, Markus | Perini, Rodolfo F. | Bajorin, Dean F. | Sharma, Padmanee | Callahan, Margaret K. | Calvo, Emiliano | Kim, Joseph W. | de Braud, Filipo | Ott, Patrick A. | Bono, Petri | Pillai, Rathi N. | Morse, Michael | Le, Dung T. | Taylor, Matthew | Spilliopoulou, Pavlina | Bendell, Johanna | Jaeger, Dirk | Chan, Emily | Antonia, Scott J. | Ascierto, Paolo A. | Hennicken, Delphine | Tschaika, Marina | Azrilevich, Alex | Rosenberg, Jonathan | Levy, Ofer | Chan, Christopher | Cojocaru, Gady | Liang, Spencer | Ophir, Eran | Ganguly, Sudipto | Toporik, Amir | Kotturi, Maya | Kfir, Tal Fridman | Murter, Benjamin M. | Logronio, Kathryn | Dassa, Liat | Leung, Ling | Greenwald, Shirley | Azulay, Meir | Kumar, Sandeep | Alteber, Zoya | Pan, Xiaoyu | Machlenkin, Arthur | Benita, Yair | Drake, Andrew W. | Chajut, Ayelet | Salomon, Ran | Vankin, Ilan | Safyon, Einav | Hunter, John | Levine, Zurit | White, Mark | Leidner, Rom | Kang, Hyunseok | Haddad, Robert | Segal, Neil H. | Wirth, Lori J. | Ferris, Robert L. | Hodi, F. Stephen | Sanborn, Rachel E. | Gajewski, Thomas F. | Sharfman, William | McDonald, Dan | Srivastava, Shivani | Gu, Xuemin | Phillips, Penny | Passey, Chaitali | Seiwert, Tanguy | Habtetsion, Tsadik | Zhou, Gang | Sakellariou-Thompson, Donastas | Haymaker, Cara | Creasy, Caitlin | Hurd, Mark | Uraoka, Naohiro | Canales, Jaime Rodriguez | Koptez, Scott | Hwu, Patrick | Maitra, Anirban | Bernatchez, Chantale | Coyle, Scott M. | Roybel, Kole T. | Rupp, Levi J. | Santoro, Stephen P. | Secrest, Stephanie | Spelman, Michael | Ho, Hanson | Gomes, Tina | Tse, Tiffany | Yung-Wu, Chia | Taunton, Jack | Lim, Wendell | Emtage, Peter | Moudgil, Tarsem | Ballesteros-Merino, Carmen | Hilton, Traci | Paustian, Christopher | Leidner, Rom | Page, David | Urba, Walter | Fox, Bernard | Bell, Bryan | Patel, Ashish | Olafsen, Tove | Satpayev, Daulet | Torgov, Michael | Marchioni, Filippo | Romero, Jason | Jiang, Ziyue Karen | Zamilpa, Charles | Keppler, Jennifer S. | Mascioni, Alessandro | Jia, Fang | Lee, Chen-Yu | Gudas, Jean | Sullivan, Ryan J. | Hoshida, Yujin | Logan, Theodore | Khushalani, Nikhil | Giobbie-Hurder, Anita | Margolin, Kim | Roder, Joanna | Bhatt, Rupal | Koon, Henry | Olencki, Thomas | Hutson, Thomas | Curti, Brendan | Blackmon, Shauna | Mier, James W. | Puzanov, Igor | Roder, Heinrich | Stewart, John | Amin, Asim | Ernstoff, Marc S. | Clark, Joseph I. | Atkins, Michael B. | Kaufman, Howard L. | Sosman, Jeffrey | Signoretti, Sabina | McDermott, David F. | Anderson, Abraham A. | Puzanov, Igor | Milhem, Mohammed M. | Andtbacka, Robert H. I. | Minor, David | Gorski, Kevin S. | Baker, Daniel M. | Hamid, Omid | Kaufman, Howard L. | Akporiaye, Emmanuel | Curti, Brendan | Koguchi, Yoshinobu | Leidner, Rom | Sutcliffe, Kim | Conder, Kristie | Urba, Walter | Marron, Thomas | Bhardwaj, Nina | Hammerich, Linda | George, Fiby | Kim-Schulze, Seunghee | Keler, Tibor | Davis, Tom | Crowley, Elizabeth | Salazar, Andres | Brody, Joshua | Monjazeb, Arta | Daly, Megan E. | Riess, Jonathan | Li, Tianhong | Murphy, William J. | Kelly, Karen | Hu, Zhiwei | Shen, Rulong | Campbell, Amanda | McMichael, Elizabeth | Yu, Lianbo | Ramaswam, Bhuvaneswari | London, Cheryl A. | Xu, Tian | Carson, William | Kokolus, Kathleen M. | Repasky, Elizabeth A. | Schell, Todd D. | Drabick, Joseph D. | Messenheimer, David J. | Jensen, Shawn | Fox, Bernard | Rubinstein, Mark | Andrijauskaite, Kristina | Swiderska-syn, Marzena | Lind, Kristin | Choppin, Agnes | Roell, Marina K. | Wrangle, John | Andrijauskaite, Kristina | Swiderska-syn, Marzena | Rhode, Peter | Wong, Hing | Rubinstein, Mark | Ahmad, Shamim | Webb, Mason | Abu-Eid, Rasha | Shrimali, Rajeev | Verma, Vivek | Doroodchi, Atbin | Berrong, Zuzana | Yashar, David | Samara, Raed | Mkrtichyan, Mikayel | Khleif, Samir | Powell, Steven | Gitau, Mark | Sumey, Christopher | Terrell, Andrew | Lohr, Michele | Nowak, Ryan K. | McGraw, Steven | Jensen, Ash | Blanchard, Miran | Gold, Kathryn A. | Cohen, Ezra E. W. | Ellison, Christie | Black, Lora | Lee, John | Spanos, William Chad | Wennerberg, Erik | Schwitzer, Emily | Lhuillier, Claire | Koelwyn, Graeme | Hiner, Rebecca | Jones, Lee | Demaria, Sandra | Amanda, Vandeveer | Greiner, John W. | Schlom, Jeffrey | Bookstaver, Michelle | Jewell, Christopher M. | Paustian, Christopher | Gunderson, Andrew | Boulmay, Brian | Li, Rui | Spieler, Bradley | Happel, Kyle | Moudgil, Tarsem | Feng, Zipei | Ballesteros-Merino, Carmen | Dubay, Christopher | Fisher, Brenda | Koguchi, Yoshinobu | Aung, Sandra | Mederos, Eileen | Bifulco, Carlo B. | McNamara, Michael | Bahjat, Keith | Redmond, William | Ochoa, Augusto | Hu, Hong-Ming | Mehta, Adi | Lund-Johansen, Fridtjof | Fox, Bernard | Urba, Walter | Sanborn, Rachel E. | Hilton, Traci | Bedu-Addo, Frank | Conn, Greg | King, Michael | Dutta, Panna | Shepard, Robert | Einstein, Mark | Adams, Sylvia | Wang, Ena | Jin, Ping | Novik, Yelena | Morrison, Debra | Oratz, Ruth | Marincola, Franco M. | Stroncek, David | Goldberg, Judith | Demaria, Sandra | Formenti, Silvia C. | Galon, Jérôme | Mlecnik, Bernhard | Marliot, Florence | Ou, Fang-Shu | Bifulco, Carlo B. | Lugli, Alessandro | Zlobec, Inti | Rau, Tilman T. | Nagtegaal, Iris D. | Vink-Borger, Elisa | Hartmann, Arndt | Geppert, Carol | Roehrl, Michael H. | Bavi, Prashant | Ohashi, Pamela S. | Wang, Julia Y. | Nguyen, Linh T. | Han, SeongJun | MacGregor, Heather L. | Hafezi-Bakhtiari, Sara | Wouters, Bradley G. | Kawakami, Yutaka | Papivanova, Boryana | Xu, Mingli | Fujita, Tomonobu | Hazama, Shoichi | Suzuki, Nobuaki | Nagano, Hiroaki | Okuno, Kiyotaka | Itoh, Kyogo | Zavadova, Eva | Vocka, Michal | Spacek, Jan | Petruzelka, Lubos | Konopasek, Bohuslav | Dundr, Pavel | Skalova, Helena | Torigoe, Toshihiko | Sato, Noriyuki | Furuhata, Tomohisa | Takemasa, Ichiro | Van den Eynde, Marc | Jouret-Mourin, Anne | Machiels, Jean-Pascal | Fredriksen, Tessa | Lafontaine, Lucie | Buttard, Bénédicte | Church, Sarah | Maby, Pauline | Angell, Helen | Angelova, Mihaela | Vasaturo, Angela | Bindea, Gabriela | Berger, Anne | Lagorce, Christine | Patel, Prabhu S. | Vora, Hemangini H. | Shah, Birva | Patel, Jayendrakumar B. | Rajvik, Kruti N. | Pandya, Shashank J. | Shukla, Shilin N. | Wang, Yili | Zhang, Guanjun | Masucci, Giuseppe V. | Andersson, Emilia K. | Grizzi, Fabio | Laghi, Luigi | Botti, Gerardo | Tatangelo, Fabiana | Delrio, Paolo | Cilberto, Gennaro | Ascierto, Paolo A. | Marincola, Franco | Sargent, Daniel J. | Fox, Bernard A. | Algazi, Alain | Tsai, Katy | Rosenblum, Michael | Nandoskar, Prachi | Andtbacka, Robert H. I. | Li, Amy | Nonomura, John | Takamura, Kathryn | Dwyer, Mary | Browning, Erica | Talia, Reneta | Twitty, Chris | Gargosky, Sharron | Campbell, Jean | Ballesteros-Merino, Carmen | Bifulco, Carlo B. | Fox, Bernard | Le, Mai | Pierce, Robert H. | Daud, Adil | Gartrell, Robyn | Marks, Douglas | Stack, Edward | Lu, Yan | Izaki, Daisuke | Beck, Kristen | Jia, Dan Tong | Armenta, Paul | White-Stern, Ashley | Fu, Yichun | Blake, Zoe | Kaufman, Howard L. | Taback, Bret | Horst, Basil | Saenger, Yvonne M. | Leonardo, Steven | Gorden, Keith | Fulton, Ross B. | Fraser, Kathryn | Kangas, Takashi O. | Walsh, Richard | Ertelt, Kathleen | Graff, Jeremy | Uhlik, Mark | Sims, Jennifer S. | Lei, Liang | Tsujiuchi, Takashi | Bruce, Jeffrey N. | Canoll, Peter | Tolcher, Anthony W | Alley, Evan W | Chichili, Gurunadh | Canoll, Jan E | Moore, Paul | Bonvini, Ezio | Johnson, Syd | Shankar, Sadhna | Vasselli, James | Wigginton, Jon | Powderly, John
doi:10.1186/s40425-016-0191-4
PMCID: PMC5260784
10.  31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two 
Ager, Casey | Reilley, Matthew | Nicholas, Courtney | Bartkowiak, Todd | Jaiswal, Ashvin | Curran, Michael | Albershardt, Tina C. | Bajaj, Anshika | Archer, Jacob F. | Reeves, Rebecca S. | Ngo, Lisa Y. | Berglund, Peter | ter Meulen, Jan | Denis, Caroline | Ghadially, Hormas | Arnoux, Thomas | Chanuc, Fabien | Fuseri, Nicolas | Wilkinson, Robert W. | Wagtmann, Nicolai | Morel, Yannis | Andre, Pascale | Atkins, Michael B. | Carlino, Matteo S. | Ribas, Antoni | Thompson, John A. | Choueiri, Toni K. | Hodi, F. Stephen | Hwu, Wen-Jen | McDermott, David F. | Atkinson, Victoria | Cebon, Jonathan S. | Fitzharris, Bernie | Jameson, Michael B. | McNeil, Catriona | Hill, Andrew G. | Mangin, Eric | Ahamadi, Malidi | van Vugt, Marianne | van Zutphen, Mariëlle | Ibrahim, Nageatte | Long, Georgina V. | Gartrell, Robyn | Blake, Zoe | Simoes, Ines | Fu, Yichun | Saito, Takuro | Qian, Yingzhi | Lu, Yan | Saenger, Yvonne M. | Budhu, Sadna | De Henau, Olivier | Zappasodi, Roberta | Schlunegger, Kyle | Freimark, Bruce | Hutchins, Jeff | Barker, Christopher A. | Wolchok, Jedd D. | Merghoub, Taha | Burova, Elena | Allbritton, Omaira | Hong, Peter | Dai, Jie | Pei, Jerry | Liu, Matt | Kantrowitz, Joel | Lai, Venus | Poueymirou, William | MacDonald, Douglas | Ioffe, Ella | Mohrs, Markus | Olson, William | Thurston, Gavin | Capasso, Cristian | Frascaro, Federica | Carpi, Sara | Tähtinen, Siri | Feola, Sara | Fusciello, Manlio | Peltonen, Karita | Martins, Beatriz | Sjöberg, Madeleine | Pesonen, Sari | Ranki, Tuuli | Kyruk, Lukasz | Ylösmäki, Erkko | Cerullo, Vincenzo | Cerignoli, Fabio | Xi, Biao | Guenther, Garret | Yu, Naichen | Muir, Lincoln | Zhao, Leyna | Abassi, Yama | Cervera-Carrascón, Víctor | Siurala, Mikko | Santos, João | Havunen, Riikka | Parviainen, Suvi | Hemminki, Akseli | Dalgleish, Angus | Mudan, Satvinder | DeBenedette, Mark | Plachco, Ana | Gamble, Alicia | Grogan, Elizabeth W. | Krisko, John | Tcherepanova, Irina | Nicolette, Charles | Dhupkar, Pooja | Yu, Ling | Kleinerman, Eugenie S. | Gordon, Nancy | Grenga, Italia | Lepone, Lauren | Gameiro, Sofia | Knudson, Karin M. | Fantini, Massimo | Tsang, Kwong | Hodge, James | Donahue, Renee | Schlom, Jeffrey | Evans, Elizabeth | Bussler, Holm | Mallow, Crystal | Reilly, Christine | Torno, Sebold | Scrivens, Maria | Foster, Cathie | Howell, Alan | Balch, Leslie | Knapp, Alyssa | Leonard, John E. | Paris, Mark | Fisher, Terry | Hu-Lieskovan, Siwen | Ribas, Antoni | Smith, Ernest | Zauderer, Maurice | Fogler, William | Franklin, Marilyn | Thayer, Matt | Saims, Dan | Magnani, John L. | Gong, Jian | Gray, Michael | Hutchins, Jeff | Freimark, Bruce | Fromm, George | de Silva, Suresh | Giffin, Louise | Xu, Xin | Rose, Jason | Schreiber, Taylor H. | Fantini, Massimo | Gameiro, Sofia R. | Knudson, Karin M. | Clavijo, Paul E. | Allen, Clint T. | Donahue, Renee | Lepone, Lauren | Grenga, Italia | Hodge, James W. | Tsang, Kwong Y. | Schlom, Jeffrey | Gray, Michael | Gong, Jian | Hutchins, Jeff | Freimark, Bruce | Grogan, Jane | Manieri, Nicholas | Chiang, Eugene | Caplazi, Patrick | Yadav, Mahesh | Hagner, Patrick | Chiu, Hsiling | Waldman, Michelle | Klippel, Anke | Thakurta, Anjan | Pourdehnad, Michael | Gandhi, Anita | Henrich, Ian | Quick, Laura | Young, Rob | Chou, Margaret | Hotson, Andrew | Willingham, Stephen | Ho, Po | Choy, Carmen | Laport, Ginna | McCaffery, Ian | Miller, Richard | Tipton, Kimberly A. | Wong, Kenneth R. | Singson, Victoria | Wong, Chihunt | Chan, Chanty | Huang, Yuanhiu | Liu, Shouchun | Richardson, Jennifer H. | Kavanaugh, W. Michael | West, James | Irving, Bryan A. | Tipton, Kimberly A. | Wong, Kenneth R. | Singson, Victoria | Wong, Chihunt | Chan, Chanty | Huang, Yuanhiu | Liu, Shouchun | Richardson, Jennifer H. | Kavanaugh, W. Michael | West, James | Irving, Bryan A. | Jaini, Ritika | Loya, Matthew | Eng, Charis | Johnson, Melissa L. | Adjei, Alex A. | Opyrchal, Mateusz | Ramalingam, Suresh | Janne, Pasi A. | Dominguez, George | Gabrilovich, Dmitry | de Leon, Laura | Hasapidis, Jeannette | Diede, Scott J. | Ordentlich, Peter | Cruickshank, Scott | Meyers, Michael L. | Hellmann, Matthew D. | Kalinski, Pawel | Zureikat, Amer | Edwards, Robert | Muthuswamy, Ravi | Obermajer, Nataša | Urban, Julie | Butterfield, Lisa H. | Gooding, William | Zeh, Herbert | Bartlett, David | Zubkova, Olga | Agapova, Larissa | Kapralova, Marina | Krasovskaia, Liudmila | Ovsepyan, Armen | Lykov, Maxim | Eremeev, Artem | Bokovanov, Vladimir | Grigoryeva, Olga | Karpov, Andrey | Ruchko, Sergey | Nicolette, Charles | Shuster, Alexandr | Khalil, Danny N. | Campesato, Luis Felipe | Li, Yanyun | Merghoub, Taha | Wolchok, Jedd D. | Lazorchak, Adam S. | Patterson, Troy D. | Ding, Yueyun | Sasikumar, Pottayil | Sudarshan, Naremaddepalli | Gowda, Nagaraj | Ramachandra, Raghuveer | Samiulla, Dodheri | Giri, Sanjeev | Eswarappa, Rajesh | Ramachandra, Murali | Tuck, David | Wyant, Timothy | Leshem, Jasmin | Liu, Xiu-fen | Bera, Tapan | Terabe, Masaki | Bossenmaier, Birgit | Niederfellner, Gerhard | Reiter, Yoram | Pastan, Ira | Xia, Leiming | Xia, Yang | Hu, Yangyang | Wang, Yi | Bao, Yangyi | Dai, Fu | Huang, Shiang | Hurt, Elaine | Hollingsworth, Robert E. | Lum, Lawrence G. | Chang, Alfred E. | Wicha, Max S. | Li, Qiao | Mace, Thomas | Makhijani, Neil | Talbert, Erin | Young, Gregory | Guttridge, Denis | Conwell, Darwin | Lesinski, Gregory B. | Gonzales, Rodney JM Macedo | Huffman, Austin P. | Wang, Ximi K. | Reshef, Ran | MacKinnon, Andy | Chen, Jason | Gross, Matt | Marguier, Gisele | Shwonek, Peter | Sotirovska, Natalija | Steggerda, Susanne | Parlati, Francesco | Makkouk, Amani | Bennett, Mark K. | Chen, Jason | Emberley, Ethan | Gross, Matt | Huang, Tony | Li, Weiqun | MacKinnon, Andy | Marguier, Gisele | Neou, Silinda | Pan, Alison | Zhang, Jing | Zhang, Winter | Parlati, Francesco | Marshall, Netonia | Marron, Thomas U. | Agudo, Judith | Brown, Brian | Brody, Joshua | McQuinn, Christopher | Mace, Thomas | Farren, Matthew | Komar, Hannah | Shakya, Reena | Young, Gregory | Ludwug, Thomas | Lesinski, Gregory B. | Morillon, Y. Maurice | Hammond, Scott A. | Schlom, Jeffrey | Greiner, John W. | Nath, Pulak R. | Schwartz, Anthony L. | Maric, Dragan | Roberts, David D. | Obermajer, Nataša | Bartlett, David | Kalinski, Pawel | Naing, Aung | Papadopoulos, Kyriakos P. | Autio, Karen A. | Wong, Deborah J. | Patel, Manish | Falchook, Gerald | Pant, Shubham | Ott, Patrick A. | Whiteside, Melinda | Patnaik, Amita | Mumm, John | Janku, Filip | Chan, Ivan | Bauer, Todd | Colen, Rivka | VanVlasselaer, Peter | Brown, Gail L. | Tannir, Nizar M. | Oft, Martin | Infante, Jeffrey | Lipson, Evan | Gopal, Ajay | Neelapu, Sattva S. | Armand, Philippe | Spurgeon, Stephen | Leonard, John P. | Hodi, F. Stephen | Sanborn, Rachel E. | Melero, Ignacio | Gajewski, Thomas F. | Maurer, Matthew | Perna, Serena | Gutierrez, Andres A. | Clynes, Raphael | Mitra, Priyam | Suryawanshi, Satyendra | Gladstone, Douglas | Callahan, Margaret K. | Crooks, James | Brown, Sheila | Gauthier, Audrey | de Boisferon, Marc Hillairet | MacDonald, Andrew | Brunet, Laura Rosa | Rothwell, William T. | Bell, Peter | Wilson, James M. | Sato-Kaneko, Fumi | Yao, Shiyin | Zhang, Shannon S. | Carson, Dennis A. | Guiducci, Cristina | Coffman, Robert L. | Kitaura, Kazutaka | Matsutani, Takaji | Suzuki, Ryuji | Hayashi, Tomoko | Cohen, Ezra E. W. | Schaer, David | Li, Yanxia | Dobkin, Julie | Amatulli, Michael | Hall, Gerald | Doman, Thompson | Manro, Jason | Dorsey, Frank Charles | Sams, Lillian | Holmgaard, Rikke | Persaud, Krishnadatt | Ludwig, Dale | Surguladze, David | Kauh, John S. | Novosiadly, Ruslan | Kalos, Michael | Driscoll, Kyla | Pandha, Hardev | Ralph, Christy | Harrington, Kevin | Curti, Brendan | Sanborn, Rachel E. | Akerley, Wallace | Gupta, Sumati | Melcher, Alan | Mansfield, David | Kaufman, David R. | Schmidt, Emmett | Grose, Mark | Davies, Bronwyn | Karpathy, Roberta | Shafren, Darren | Shamalov, Katerina | Cohen, Cyrille | Sharma, Naveen | Allison, James | Shekarian, Tala | Valsesia-Wittmann, Sandrine | Caux, Christophe | Marabelle, Aurelien | Slomovitz, Brian M. | Moore, Kathleen M. | Youssoufian, Hagop | Posner, Marshall | Tewary, Poonam | Brooks, Alan D. | Xu, Ya-Ming | Wijeratne, Kithsiri | Gunatilaka, Leslie A. A. | Sayers, Thomas J. | Vasilakos, John P. | Alston, Tesha | Dovedi, Simon | Elvecrog, James | Grigsby, Iwen | Herbst, Ronald | Johnson, Karen | Moeckly, Craig | Mullins, Stefanie | Siebenaler, Kristen | SternJohn, Julius | Tilahun, Ashenafi | Tomai, Mark A. | Vogel, Katharina | Wilkinson, Robert W. | Vietsch, Eveline E. | Wellstein, Anton | Wythes, Martin | Crosignani, Stefano | Tumang, Joseph | Alekar, Shilpa | Bingham, Patrick | Cauwenberghs, Sandra | Chaplin, Jenny | Dalvie, Deepak | Denies, Sofie | De Maeseneire, Coraline | Feng, JunLi | Frederix, Kim | Greasley, Samantha | Guo, Jie | Hardwick, James | Kaiser, Stephen | Jessen, Katti | Kindt, Erick | Letellier, Marie-Claire | Li, Wenlin | Maegley, Karen | Marillier, Reece | Miller, Nichol | Murray, Brion | Pirson, Romain | Preillon, Julie | Rabolli, Virginie | Ray, Chad | Ryan, Kevin | Scales, Stephanie | Srirangam, Jay | Solowiej, Jim | Stewart, Al | Streiner, Nicole | Torti, Vince | Tsaparikos, Konstantinos | Zheng, Xianxian | Driessens, Gregory | Gomes, Bruno | Kraus, Manfred | Xu, Chunxiao | Zhang, Yanping | Kradjian, Giorgio | Qin, Guozhong | Qi, Jin | Xu, Xiaomei | Marelli, Bo | Yu, Huakui | Guzman, Wilson | Tighe, Rober | Salazar, Rachel | Lo, Kin-Ming | English, Jessie | Radvanyi, Laszlo | Lan, Yan | Zappasodi, Roberta | Budhu, Sadna | Hellmann, Matthew D. | Postow, Michael | Senbabaoglu, Yasin | Gasmi, Billel | Zhong, Hong | Li, Yanyun | Liu, Cailian | Hirschhorhn-Cymerman, Daniel | Wolchok, Jedd D. | Merghoub, Taha | Zha, Yuanyuan | Malnassy, Gregory | Fulton, Noreen | Park, Jae-Hyun | Stock, Wendy | Nakamura, Yusuke | Gajewski, Thomas F. | Liu, Hongtao | Ju, Xiaoming | Kosoff, Rachelle | Ramos, Kimberly | Coder, Brandon | Petit, Robert | Princiotta, Michael | Perry, Kyle | Zou, Jun | Arina, Ainhoa | Fernandez, Christian | Zheng, Wenxin | Beckett, Michael A. | Mauceri, Helena J. | Fu, Yang-Xin | Weichselbaum, Ralph R. | DeBenedette, Mark | Lewis, Whitney | Gamble, Alicia | Nicolette, Charles | Han, Yanyan | Wu, Yeting | Yang, Chou | Huang, Jing | Wu, Dongyun | Li, Jin | Liang, Xiaoling | Zhou, Xiangjun | Hou, Jinlin | Hassan, Raffit | Jahan, Thierry | Antonia, Scott J. | Kindler, Hedy L. | Alley, Evan W. | Honarmand, Somayeh | Liu, Weiqun | Leong, Meredith L. | Whiting, Chan C. | Nair, Nitya | Enstrom, Amanda | Lemmens, Edward E. | Tsujikawa, Takahiro | Kumar, Sushil | Coussens, Lisa M. | Murphy, Aimee L. | Brockstedt, Dirk G. | Koch, Sven D. | Sebastian, Martin | Weiss, Christian | Früh, Martin | Pless, Miklos | Cathomas, Richard | Hilbe, Wolfgang | Pall, Georg | Wehler, Thomas | Alt, Jürgen | Bischoff, Helge | Geissler, Michael | Griesinger, Frank | Kollmeier, Jens | Papachristofilou, Alexandros | Doener, Fatma | Fotin-Mleczek, Mariola | Hipp, Madeleine | Hong, Henoch S. | Kallen, Karl-Josef | Klinkhardt, Ute | Stosnach, Claudia | Scheel, Birgit | Schroeder, Andreas | Seibel, Tobias | Gnad-Vogt, Ulrike | Zippelius, Alfred | Park, Ha-Ram | Ahn, Yong-Oon | Kim, Tae Min | Kim, Soyeon | Kim, Seulki | Lee, Yu Soo | Keam, Bhumsuk | Kim, Dong-Wan | Heo, Dae Seog | Pilon-Thomas, Shari | Weber, Amy | Morse, Jennifer | Kodumudi, Krithika | Liu, Hao | Mullinax, John | Sarnaik, Amod A. | Pike, Luke | Bang, Andrew | Ott, Patrick A. | Balboni, Tracy | Taylor, Allison | Spektor, Alexander | Wilhite, Tyler | Krishnan, Monica | Cagney, Daniel | Alexander, Brian | Aizer, Ayal | Buchbinder, Elizabeth | Awad, Mark | Ghandi, Leena | Hodi, F. Stephen | Schoenfeld, Jonathan | Schwartz, Anthony L. | Nath, Pulak R. | Lessey-Morillon, Elizabeth | Ridnour, Lisa | Roberts, David D. | Segal, Neil H. | Sharma, Manish | Le, Dung T. | Ott, Patrick A. | Ferris, Robert L. | Zelenetz, Andrew D. | Neelapu, Sattva S. | Levy, Ronald | Lossos, Izidore S. | Jacobson, Caron | Ramchandren, Radhakrishnan | Godwin, John | Colevas, A. Dimitrios | Meier, Roland | Krishnan, Suba | Gu, Xuemin | Neely, Jaclyn | Suryawanshi, Satyendra | Timmerman, John | Vanpouille-Box, Claire I. | Formenti, Silvia C. | Demaria, Sandra | Wennerberg, Erik | Mediero, Aranzazu | Cronstein, Bruce N. | Formenti, Silvia C. | Demaria, Sandra | Gustafson, Michael P. | DiCostanzo, AriCeli | Wheatley, Courtney | Kim, Chul-Ho | Bornschlegl, Svetlana | Gastineau, Dennis A. | Johnson, Bruce D. | Dietz, Allan B. | MacDonald, Cameron | Bucsek, Mark | Qiao, Guanxi | Hylander, Bonnie | Repasky, Elizabeth | Turbitt, William J. | Xu, Yitong | Mastro, Andrea | Rogers, Connie J. | Withers, Sita | Wang, Ziming | Khuat, Lam T. | Dunai, Cordelia | Blazar, Bruce R. | Longo, Dan | Rebhun, Robert | Grossenbacher, Steven K. | Monjazeb, Arta | Murphy, William J. | Rowlinson, Scott | Agnello, Giulia | Alters, Susan | Lowe, David | Scharping, Nicole | Menk, Ashley V. | Whetstone, Ryan | Zeng, Xue | Delgoffe, Greg M. | Santos, Patricia M. | Menk, Ashley V. | Shi, Jian | Delgoffe, Greg M. | Butterfield, Lisa H. | Whetstone, Ryan | Menk, Ashley V. | Scharping, Nicole | Delgoffe, Greg | Nagasaka, Misako | Sukari, Ammar | Byrne-Steele, Miranda | Pan, Wenjing | Hou, Xiaohong | Brown, Brittany | Eisenhower, Mary | Han, Jian | Collins, Natalie | Manguso, Robert | Pope, Hans | Shrestha, Yashaswi | Boehm, Jesse | Haining, W. Nicholas | Cron, Kyle R. | Sivan, Ayelet | Aquino-Michaels, Keston | Gajewski, Thomas F. | Orecchioni, Marco | Bedognetti, Davide | Hendrickx, Wouter | Fuoco, Claudia | Spada, Filomena | Sgarrella, Francesco | Cesareni, Gianni | Marincola, Francesco | Kostarelos, Kostas | Bianco, Alberto | Delogu, Lucia | Hendrickx, Wouter | Roelands, Jessica | Boughorbel, Sabri | Decock, Julie | Presnell, Scott | Wang, Ena | Marincola, Franco M. | Kuppen, Peter | Ceccarelli, Michele | Rinchai, Darawan | Chaussabel, Damien | Miller, Lance | Bedognetti, Davide | Nguyen, Andrew | Sanborn, J. Zachary | Vaske, Charles | Rabizadeh, Shahrooz | Niazi, Kayvan | Benz, Steven | Patel, Shashank | Restifo, Nicholas | White, James | Angiuoli, Sam | Sausen, Mark | Jones, Sian | Sevdali, Maria | Simmons, John | Velculescu, Victor | Diaz, Luis | Zhang, Theresa | Sims, Jennifer S. | Barton, Sunjay M. | Gartrell, Robyn | Kadenhe-Chiweshe, Angela | Dela Cruz, Filemon | Turk, Andrew T. | Lu, Yan | Mazzeo, Christopher F. | Kung, Andrew L. | Bruce, Jeffrey N. | Saenger, Yvonne M. | Yamashiro, Darrell J. | Connolly, Eileen P. | Baird, Jason | Crittenden, Marka | Friedman, David | Xiao, Hong | Leidner, Rom | Bell, Bryan | Young, Kristina | Gough, Michael | Bian, Zhen | Kidder, Koby | Liu, Yuan | Curran, Emily | Chen, Xiufen | Corrales, Leticia P. | Kline, Justin | Dunai, Cordelia | Aguilar, Ethan G. | Khuat, Lam T. | Murphy, William J. | Guerriero, Jennifer | Sotayo, Alaba | Ponichtera, Holly | Pourzia, Alexandra | Schad, Sara | Carrasco, Ruben | Lazo, Suzan | Bronson, Roderick | Letai, Anthony | Kornbluth, Richard S. | Gupta, Sachin | Termini, James | Guirado, Elizabeth | Stone, Geoffrey W. | Meyer, Christina | Helming, Laura | Tumang, Joseph | Wilson, Nicholas | Hofmeister, Robert | Radvanyi, Laszlo | Neubert, Natalie J. | Tillé, Laure | Barras, David | Soneson, Charlotte | Baumgaertner, Petra | Rimoldi, Donata | Gfeller, David | Delorenzi, Mauro | Fuertes Marraco, Silvia A. | Speiser, Daniel E. | Abraham, Tara S. | Xiang, Bo | Magee, Michael S. | Waldman, Scott A. | Snook, Adam E. | Blogowski, Wojciech | Zuba-Surma, Ewa | Budkowska, Marta | Salata, Daria | Dolegowska, Barbara | Starzynska, Teresa | Chan, Leo | Somanchi, Srinivas | McCulley, Kelsey | Lee, Dean | Buettner, Nico | Shi, Feng | Myers, Paisley T. | Curbishley, Stuart | Penny, Sarah A. | Steadman, Lora | Millar, David | Speers, Ellen | Ruth, Nicola | Wong, Gabriel | Thimme, Robert | Adams, David | Cobbold, Mark | Thomas, Remy | Hendrickx, Wouter | Al-Muftah, Mariam | Decock, Julie | Wong, Michael KK | Morse, Michael | McDermott, David F. | Clark, Joseph I. | Kaufman, Howard L. | Daniels, Gregory A. | Hua, Hong | Rao, Tharak | Dutcher, Janice P. | Kang, Kai | Saunthararajah, Yogen | Velcheti, Vamsidhar | Kumar, Vikas | Anwar, Firoz | Verma, Amita | Chheda, Zinal | Kohanbash, Gary | Sidney, John | Okada, Kaori | Shrivastav, Shruti | Carrera, Diego A. | Liu, Shuming | Jahan, Naznin | Mueller, Sabine | Pollack, Ian F. | Carcaboso, Angel M. | Sette, Alessandro | Hou, Yafei | Okada, Hideho | Field, Jessica J. | Zeng, Weiping | Shih, Vincent FS | Law, Che-Leung | Senter, Peter D. | Gardai, Shyra J. | Okeley, Nicole M. | Penny, Sarah A. | Abelin, Jennifer G. | Saeed, Abu Z. | Malaker, Stacy A. | Myers, Paisley T. | Shabanowitz, Jeffrey | Ward, Stephen T. | Hunt, Donald F. | Cobbold, Mark | Profusek, Pam | Wood, Laura | Shepard, Dale | Grivas, Petros | Kapp, Kerstin | Volz, Barbara | Oswald, Detlef | Wittig, Burghardt | Schmidt, Manuel | Sefrin, Julian P. | Hillringhaus, Lars | Lifke, Valeria | Lifke, Alexander | Skaletskaya, Anna | Ponte, Jose | Chittenden, Thomas | Setiady, Yulius | Valsesia-Wittmann, Sandrine | Sivado, Eva | Thomas, Vincent | El Alaoui, Meddy | Papot, Sébastien | Dumontet, Charles | Dyson, Mike | McCafferty, John | El Alaoui, Said | Verma, Amita | Kumar, Vikas | Bommareddy, Praveen K. | Kaufman, Howard L. | Zloza, Andrew | Kohlhapp, Frederick | Silk, Ann W. | Jhawar, Sachin | Paneque, Tomas | Bommareddy, Praveen K. | Kohlhapp, Frederick | Newman, Jenna | Beltran, Pedro | Zloza, Andrew | Kaufman, Howard L. | Cao, Felicia | Hong, Bang-Xing | Rodriguez-Cruz, Tania | Song, Xiao-Tong | Gottschalk, Stephen | Calderon, Hugo | Illingworth, Sam | Brown, Alice | Fisher, Kerry | Seymour, Len | Champion, Brian | Eriksson, Emma | Wenthe, Jessica | Hellström, Ann-Charlotte | Paul-Wetterberg, Gabriella | Loskog, Angelica | Eriksson, Emma | Milenova, Ioanna | Wenthe, Jessica | Ståhle, Magnus | Jarblad-Leja, Justyna | Ullenhag, Gustav | Dimberg, Anna | Moreno, Rafael | Alemany, Ramon | Loskog, Angelica | Eriksson, Emma | Milenova, Ioanna | Moreno, Rafael | Alemany, Ramon
Journal for Immunotherapy of Cancer  2016;4(Suppl 1):107-221.
doi:10.1186/s40425-016-0173-6
PMCID: PMC5123381
11.  31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part one 
Lundqvist, Andreas | van Hoef, Vincent | Zhang, Xiaonan | Wennerberg, Erik | Lorent, Julie | Witt, Kristina | Sanz, Laia Masvidal | Liang, Shuo | Murray, Shannon | Larsson, Ola | Kiessling, Rolf | Mao, Yumeng | Sidhom, John-William | Bessell, Catherine A. | Havel, Jonathan | Schneck, Jonathan | Chan, Timothy A. | Sachsenmeier, Eliot | Woods, David | Berglund, Anders | Ramakrishnan, Rupal | Sodre, Andressa | Weber, Jeffrey | Zappasodi, Roberta | Li, Yanyun | Qi, Jingjing | Wong, Philip | Sirard, Cynthia | Postow, Michael | Newman, Walter | Koon, Henry | Velcheti, Vamsidhar | Callahan, Margaret K. | Wolchok, Jedd D. | Merghoub, Taha | Lum, Lawrence G. | Choi, Minsig | Thakur, Archana | Deol, Abhinav | Dyson, Gregory | Shields, Anthony | Haymaker, Cara | Uemura, Marc | Murthy, Ravi | James, Marihella | Wang, Daqing | Brevard, Julie | Monaghan, Catherine | Swann, Suzanne | Geib, James | Cornfeld, Mark | Chunduru, Srinivas | Agrawal, Sudhir | Yee, Cassian | Wargo, Jennifer | Patel, Sapna P. | Amaria, Rodabe | Tawbi, Hussein | Glitza, Isabella | Woodman, Scott | Hwu, Wen-Jen | Davies, Michael A. | Hwu, Patrick | Overwijk, Willem W. | Bernatchez, Chantale | Diab, Adi | Massarelli, Erminia | Segal, Neil H. | Ribrag, Vincent | Melero, Ignacio | Gangadhar, Tara C. | Urba, Walter | Schadendorf, Dirk | Ferris, Robert L. | Houot, Roch | Morschhauser, Franck | Logan, Theodore | Luke, Jason J. | Sharfman, William | Barlesi, Fabrice | Ott, Patrick A. | Mansi, Laura | Kummar, Shivaani | Salles, Gilles | Carpio, Cecilia | Meier, Roland | Krishnan, Suba | McDonald, Dan | Maurer, Matthew | Gu, Xuemin | Neely, Jaclyn | Suryawanshi, Satyendra | Levy, Ronald | Khushalani, Nikhil | Wu, Jennifer | Zhang, Jinyu | Basher, Fahmin | Rubinstein, Mark | Bucsek, Mark | Qiao, Guanxi | MacDonald, Cameron | Hylander, Bonnie | Repasky, Elizabeth | Chatterjee, Shilpak | Daenthanasanmak, Anusara | Chakraborty, Paramita | Toth, Kyle | Meek, Megan | Garrett-Mayer, Elizabeth | Nishimura, Michael | Paulos, Chrystal | Beeson, Craig | Yu, Xuezhong | Mehrotra, Shikhar | Zhao, Fei | Evans, Kathy | Xiao, Christine | Holtzhausen, Alisha | Hanks, Brent A. | Scharping, Nicole | Menk, Ashley V. | Moreci, Rebecca | Whetstone, Ryan | Dadey, Rebekah | Watkins, Simon | Ferris, Robert | Delgoffe, Greg M. | Peled, Jonathan | Devlin, Sean | Staffas, Anna | Lumish, Melissa | Rodriguez, Kori Porosnicu | Ahr, Katya | Perales, Miguel | Giralt, Sergio | Taur, Ying | Pamer, Eric | van den Brink, Marcel R. M. | Jenq, Robert | Annels, Nicola | Pandha, Hardev | Simpson, Guy | Mostafid, Hugh | Harrington, Kevin | Melcher, Alan | Grose, Mark | Davies, Bronwyn | Au, Gough | Karpathy, Roberta | Shafren, Darren | Ricca, Jacob | Merghoub, Taha | Wolchok, Jedd D. | Zamarin, Dmitriy | Batista, Luciana | Marliot, Florence | Vasaturo, Angela | Carpentier, Sabrina | Poggionovo, Cécile | Frayssinet, Véronique | Fieschi, Jacques | Van den Eynde, Marc | Pagès, Franck | Galon, Jérôme | Hermitte, Fabienne | Smith, Sean G. | Nguyen, Khue | Ravindranathan, Sruthi | Koppolu, Bhanu | Zaharoff, David | Schvartsman, Gustavo | Bassett, Roland | McQuade, Jennifer L. | Haydu, Lauren E. | Davies, Michael A. | Tawbi, Hussein | Glitza, Isabella | Kline, Douglas | Chen, Xiufen | Fosco, Dominick | Kline, Justin | Overacre, Abigail | Chikina, Maria | Brunazzi, Erin | Shayan, Gulidanna | Horne, William | Kolls, Jay | Ferris, Robert L. | Delgoffe, Greg M. | Bruno, Tullia C. | Workman, Creg | Vignali, Dario | Adusumilli, Prasad S. | Ansa-Addo, Ephraim A | Li, Zihai | Gerry, Andrew | Sanderson, Joseph P. | Howe, Karen | Docta, Roslin | Gao, Qian | Bagg, Eleanor A. L. | Tribble, Nicholas | Maroto, Miguel | Betts, Gareth | Bath, Natalie | Melchiori, Luca | Lowther, Daniel E. | Ramachandran, Indu | Kari, Gabor | Basu, Samik | Binder-Scholl, Gwendolyn | Chagin, Karen | Pandite, Lini | Holdich, Tom | Amado, Rafael | Zhang, Hua | Glod, John | Bernstein, Donna | Jakobsen, Bent | Mackall, Crystal | Wong, Ryan | Silk, Jonathan D. | Adams, Katherine | Hamilton, Garth | Bennett, Alan D. | Brett, Sara | Jing, Junping | Quattrini, Adriano | Saini, Manoj | Wiedermann, Guy | Gerry, Andrew | Jakobsen, Bent | Binder-Scholl, Gwendolyn | Brewer, Joanna | Duong, MyLinh | Lu, An | Chang, Peter | Mahendravada, Aruna | Shinners, Nicholas | Slawin, Kevin | Spencer, David M. | Foster, Aaron E. | Bayle, J. Henri | Bergamaschi, Cristina | Ng, Sinnie Sin Man | Nagy, Bethany | Jensen, Shawn | Hu, Xintao | Alicea, Candido | Fox, Bernard | Felber, Barbara | Pavlakis, George | Chacon, Jessica | Yamamoto, Tori | Garrabrant, Thomas | Cortina, Luis | Powell, Daniel J. | Donia, Marco | Kjeldsen, Julie Westerlin | Andersen, Rikke | Westergaard, Marie Christine Wulff | Bianchi, Valentina | Legut, Mateusz | Attaf, Meriem | Dolton, Garry | Szomolay, Barbara | Ott, Sascha | Lyngaa, Rikke | Hadrup, Sine Reker | Sewell, Andrew Kelvin | Svane, Inge Marie | Fan, Aaron | Kumai, Takumi | Celis, Esteban | Frank, Ian | Stramer, Amanda | Blaskovich, Michelle A. | Wardell, Seth | Fardis, Maria | Bender, James | Lotze, Michael T. | Goff, Stephanie L. | Zacharakis, Nikolaos | Assadipour, Yasmine | Prickett, Todd D. | Gartner, Jared J. | Somerville, Robert | Black, Mary | Xu, Hui | Chinnasamy, Harshini | Kriley, Isaac | Lu, Lily | Wunderlich, John | Robbins, Paul F. | Rosenberg, Steven | Feldman, Steven A. | Trebska-McGowan, Kasia | Kriley, Isaac | Malekzadeh, Parisa | Payabyab, Eden | Sherry, Richard | Rosenberg, Steven | Goff, Stephanie L. | Gokuldass, Aishwarya | Blaskovich, Michelle A. | Kopits, Charlene | Rabinovich, Brian | Lotze, Michael T. | Green, Daniel S. | Kamenyeva, Olena | Zoon, Kathryn C. | Annunziata, Christina M. | Hammill, Joanne | Helsen, Christopher | Aarts, Craig | Bramson, Jonathan | Harada, Yui | Yonemitsu, Yoshikazu | Helsen, Christopher | Hammill, Joanne | Mwawasi, Kenneth | Denisova, Galina | Bramson, Jonathan | Giri, Rajanish | Jin, Benjamin | Campbell, Tracy | Draper, Lindsey M. | Stevanovic, Sanja | Yu, Zhiya | Weissbrich, Bianca | Restifo, Nicholas P. | Trimble, Cornelia L. | Rosenberg, Steven | Hinrichs, Christian S. | Tsang, Kwong | Fantini, Massimo | Hodge, James W. | Fujii, Rika | Fernando, Ingrid | Jochems, Caroline | Heery, Christopher | Gulley, James | Soon-Shiong, Patrick | Schlom, Jeffrey | Jing, Weiqing | Gershan, Jill | Blitzer, Grace | Weber, James | McOlash, Laura | Johnson, Bryon D. | Kiany, Simin | Gangxiong, Huang | Kleinerman, Eugenie S. | Klichinsky, Michael | Ruella, Marco | Shestova, Olga | Kenderian, Saad | Kim, Miriam | Scholler, John | June, Carl H. | Gill, Saar | Moogk, Duane | Zhong, Shi | Yu, Zhiya | Liadi, Ivan | Rittase, William | Fang, Victoria | Dougherty, Janna | Perez-Garcia, Arianne | Osman, Iman | Zhu, Cheng | Varadarajan, Navin | Restifo, Nicholas P. | Frey, Alan | Krogsgaard, Michelle | Landi, Daniel | Fousek, Kristen | Mukherjee, Malini | Shree, Ankita | Joseph, Sujith | Bielamowicz, Kevin | Byrd, Tiara | Ahmed, Nabil | Hegde, Meenakshi | Lee, Sylvia | Byrd, David | Thompson, John | Bhatia, Shailender | Tykodi, Scott | Delismon, Judy | Chu, Liz | Abdul-Alim, Siddiq | Ohanian, Arpy | DeVito, Anna Marie | Riddell, Stanley | Margolin, Kim | Magalhaes, Isabelle | Mattsson, Jonas | Uhlin, Michael | Nemoto, Satoshi | Villarroel, Patricio Pérez | Nakagawa, Ryosuke | Mule, James J. | Mailloux, Adam W. | Mata, Melinda | Nguyen, Phuong | Gerken, Claudia | DeRenzo, Christopher | Spencer, David M. | Gottschalk, Stephen | Mathieu, Mélissa | Pelletier, Sandy | Stagg, John | Turcotte, Simon | Minutolo, Nicholas | Sharma, Prannda | Tsourkas, Andrew | Powell, Daniel J. | Mockel-Tenbrinck, Nadine | Mauer, Daniela | Drechsel, Katharina | Barth, Carola | Freese, Katharina | Kolrep, Ulrike | Schult, Silke | Assenmacher, Mario | Kaiser, Andrew | Mullinax, John | Hall, MacLean | Le, Julie | Kodumudi, Krithika | Royster, Erica | Richards, Allison | Gonzalez, Ricardo | Sarnaik, Amod | Pilon-Thomas, Shari | Nielsen, Morten | Krarup-Hansen, Anders | Hovgaard, Dorrit | Petersen, Michael Mørk | Loya, Anand Chainsukh | Junker, Niels | Svane, Inge Marie | Rivas, Charlotte | Parihar, Robin | Gottschalk, Stephen | Rooney, Cliona M. | Qin, Haiying | Nguyen, Sang | Su, Paul | Burk, Chad | Duncan, Brynn | Kim, Bong-Hyun | Kohler, M. Eric | Fry, Terry | Rao, Arjun A. | Teyssier, Noam | Pfeil, Jacob | Sgourakis, Nikolaos | Salama, Sofie | Haussler, David | Richman, Sarah A. | Nunez-Cruz, Selene | Gershenson, Zack | Mourelatos, Zissimos | Barrett, David | Grupp, Stephan | Milone, Michael | Rodriguez-Garcia, Alba | Robinson, Matthew K. | Adams, Gregory P. | Powell, Daniel J. | Santos, João | Havunen, Riikka | Siurala, Mikko | Cervera-Carrascón, Víctor | Parviainen, Suvi | Antilla, Marjukka | Hemminki, Akseli | Sethuraman, Jyothi | Santiago, Laurelis | Chen, Jie Qing | Dai, Zhimin | Wardell, Seth | Bender, James | Lotze, Michael T. | Sha, Huizi | Su, Shu | Ding, Naiqing | Liu, Baorui | Stevanovic, Sanja | Pasetto, Anna | Helman, Sarah R. | Gartner, Jared J. | Prickett, Todd D. | Robbins, Paul F. | Rosenberg, Steven A. | Hinrichs, Christian S. | Bhatia, Shailender | Burgess, Melissa | Zhang, Hui | Lee, Tien | Klingemann, Hans | Soon-Shiong, Patrick | Nghiem, Paul | Kirkwood, John M. | Rossi, John M. | Sherman, Marika | Xue, Allen | Shen, Yueh-wei | Navale, Lynn | Rosenberg, Steven A. | Kochenderfer, James N. | Bot, Adrian | Veerapathran, Anandaraman | Gokuldass, Aishwarya | Stramer, Amanda | Sethuraman, Jyothi | Blaskovich, Michelle A. | Wiener, Doris | Frank, Ian | Santiago, Laurelis | Rabinovich, Brian | Fardis, Maria | Bender, James | Lotze, Michael T. | Waller, Edmund K. | Li, Jian-Ming | Petersen, Christopher | Blazar, Bruce R. | Li, Jingxia | Giver, Cynthia R. | Wang, Ziming | Grossenbacher, Steven K. | Sturgill, Ian | Canter, Robert J. | Murphy, William J. | Zhang, Congcong | Burger, Michael C. | Jennewein, Lukas | Waldmann, Anja | Mittelbronn, Michel | Tonn, Torsten | Steinbach, Joachim P. | Wels, Winfried S. | Williams, Jason B. | Zha, Yuanyuan | Gajewski, Thomas F. | Williams, LaTerrica C. | Krenciute, Giedre | Kalra, Mamta | Louis, Chrystal | Gottschalk, Stephen | Xin, Gang | Schauder, David | Jiang, Aimin | Joshi, Nikhil | Cui, Weiguo | Zeng, Xue | Menk, Ashley V. | Scharping, Nicole | Delgoffe, Greg M. | Zhao, Zeguo | Hamieh, Mohamad | Eyquem, Justin | Gunset, Gertrude | Bander, Neil | Sadelain, Michel | Askmyr, David | Abolhalaj, Milad | Lundberg, Kristina | Greiff, Lennart | Lindstedt, Malin | Angell, Helen K. | Kim, Kyoung-Mee | Kim, Seung-Tae | Kim, Sung | Sharpe, Alan D. | Ogden, Julia | Davenport, Anna | Hodgson, Darren R. | Barrett, Carl | Lee, Jeeyun | Kilgour, Elaine | Hanson, Jodi | Caspell, Richard | Karulin, Alexey | Lehmann, Paul | Ansari, Tameem | Schiller, Annemarie | Sundararaman, Srividya | Lehmann, Paul | Hanson, Jodi | Roen, Diana | Karulin, Alexey | Lehmann, Paul | Ayers, Mark | Levitan, Diane | Arreaza, Gladys | Liu, Fang | Mogg, Robin | Bang, Yung-Jue | O’Neil, Bert | Cristescu, Razvan | Friedlander, Philip | Wassman, Karl | Kyi, Chrisann | Oh, William | Bhardwaj, Nina | Bornschlegl, Svetlana | Gustafson, Michael P. | Gastineau, Dennis A. | Parney, Ian F. | Dietz, Allan B. | Carvajal-Hausdorf, Daniel | Mani, Nikita | Velcheti, Vamsidhar | Schalper, Kurt | Rimm, David | Chang, Serena | Levy, Ronald | Kurland, John | Krishnan, Suba | Ahlers, Christoph Matthias | Jure-Kunkel, Maria | Cohen, Lewis | Maecker, Holden | Kohrt, Holbrook | Chen, Shuming | Crabill, George | Pritchard, Theresa | McMiller, Tracee | Pardoll, Drew | Pan, Fan | Topalian, Suzanne | Danaher, Patrick | Warren, Sarah | Dennis, Lucas | White, Andrew M. | D’Amico, Leonard | Geller, Melissa | Disis, Mary L. | Beechem, Joseph | Odunsi, Kunle | Fling, Steven | Derakhshandeh, Roshanak | Webb, Tonya J. | Dubois, Sigrid | Conlon, Kevin | Bryant, Bonita | Hsu, Jennifer | Beltran, Nancy | Müller, Jürgen | Waldmann, Thomas | Duhen, Rebekka | Duhen, Thomas | Thompson, Lucas | Montler, Ryan | Weinberg, Andrew | Kates, Max | Early, Brandon | Yusko, Erik | Schreiber, Taylor H. | Bivalacqua, Trinity J. | Ayers, Mark | Lunceford, Jared | Nebozhyn, Michael | Murphy, Erin | Loboda, Andrey | Kaufman, David R. | Albright, Andrew | Cheng, Jonathan | Kang, S. Peter | Shankaran, Veena | Piha-Paul, Sarina A. | Yearley, Jennifer | Seiwert, Tanguy | Ribas, Antoni | McClanahan, Terrill K. | Cristescu, Razvan | Mogg, Robin | Ayers, Mark | Albright, Andrew | Murphy, Erin | Yearley, Jennifer | Sher, Xinwei | Liu, Xiao Qiao | Nebozhyn, Michael | Lunceford, Jared | Joe, Andrew | Cheng, Jonathan | Plimack, Elizabeth | Ott, Patrick A. | McClanahan, Terrill K. | Loboda, Andrey | Kaufman, David R. | Forrest-Hay, Alex | Guyre, Cheryl A. | Narumiya, Kohei | Delcommenne, Marc | Hirsch, Heather A. | Deshpande, Amit | Reeves, Jason | Shu, Jenny | Zi, Tong | Michaelson, Jennifer | Law, Debbie | Trehu, Elizabeth | Sathyanaryanan, Sriram | Hodkinson, Brendan P. | Hutnick, Natalie A. | Schaffer, Michael E. | Gormley, Michael | Hulett, Tyler | Jensen, Shawn | Ballesteros-Merino, Carmen | Dubay, Christopher | Afentoulis, Michael | Reddy, Ashok | David, Larry | Fox, Bernard | Jayant, Kumar | Agrawal, Swati | Agrawal, Rajendra | Jeyakumar, Ghayathri | Kim, Seongho | Kim, Heejin | Silski, Cynthia | Suisham, Stacey | Heath, Elisabeth | Vaishampayan, Ulka | Vandeven, Natalie | Viller, Natasja Nielsen | O’Connor, Alison | Chen, Hui | Bossen, Bolette | Sievers, Eric | Uger, Robert | Nghiem, Paul | Johnson, Lisa | Kao, Hsiang-Fong | Hsiao, Chin-Fu | Lai, Shu-Chuan | Wang, Chun-Wei | Ko, Jenq-Yuh | Lou, Pei-Jen | Lee, Tsai-Jan | Liu, Tsang-Wu | Hong, Ruey-Long | Kearney, Staci J. | Black, Joshua C. | Landis, Benjamin J. | Koegler, Sally | Hirsch, Brooke | Gianani, Roberto | Kim, Jeffrey | He, Ming-Xiao | Zhang, Bingqing | Su, Nan | Luo, Yuling | Ma, Xiao-Jun | Park, Emily | Kim, Dae Won | Copploa, Domenico | Kothari, Nishi | doo Chang, Young | Kim, Richard | Kim, Namyong | Lye, Melvin | Wan, Ee | Kim, Namyong | Lye, Melvin | Wan, Ee | Kim, Namyong | Lye, Melvin | Wan, Ee | Knaus, Hanna A. | Berglund, Sofia | Hackl, Hubert | Karp, Judith E. | Gojo, Ivana | Luznik, Leo | Hong, Henoch S. | Koch, Sven D. | Scheel, Birgit | Gnad-Vogt, Ulrike | Kallen, Karl-Josef | Wiegand, Volker | Backert, Linus | Kohlbacher, Oliver | Hoerr, Ingmar | Fotin-Mleczek, Mariola | Billingsley, James M. | Koguchi, Yoshinobu | Conrad, Valerie | Miller, William | Gonzalez, Iliana | Poplonski, Tomasz | Meeuwsen, Tanisha | Howells-Ferreira, Ana | Rattray, Rogan | Campbell, Mary | Bifulco, Carlo | Dubay, Christopher | Bahjat, Keith | Curti, Brendan | Urba, Walter | Vetsika, E-K | Kallergi, G. | Aggouraki, Despoina | Lyristi, Z. | Katsarlinos, P. | Koinis, Filippos | Georgoulias, V. | Kotsakis, Athanasios | Martin, Nathan T. | Aeffner, Famke | Kearney, Staci J. | Black, Joshua C. | Cerkovnik, Logan | Pratte, Luke | Kim, Rebecca | Hirsch, Brooke | Krueger, Joseph | Gianani, Roberto | Martínez-Usatorre, Amaia | Jandus, Camilla | Donda, Alena | Carretero-Iglesia, Laura | Speiser, Daniel E. | Zehn, Dietmar | Rufer, Nathalie | Romero, Pedro | Panda, Anshuman | Mehnert, Janice | Hirshfield, Kim M. | Riedlinger, Greg | Damare, Sherri | Saunders, Tracie | Sokol, Levi | Stein, Mark | Poplin, Elizabeth | Rodriguez-Rodriguez, Lorna | Silk, Ann | Chan, Nancy | Frankel, Melissa | Kane, Michael | Malhotra, Jyoti | Aisner, Joseph | Kaufman, Howard L. | Ali, Siraj | Ross, Jeffrey | White, Eileen | Bhanot, Gyan | Ganesan, Shridar | Monette, Anne | Bergeron, Derek | Amor, Amira Ben | Meunier, Liliane | Caron, Christine | Morou, Antigoni | Kaufmann, Daniel | Liberman, Moishe | Jurisica, Igor | Mes-Masson, Anne-Marie | Hamzaoui, Kamel | Lapointe, Rejean | Mongan, Ann | Ku, Yuan-Chieh | Tom, Warren | Sun, Yongming | Pankov, Alex | Looney, Tim | Au-Young, Janice | Hyland, Fiona | Conroy, Jeff | Morrison, Carl | Glenn, Sean | Burgher, Blake | Ji, He | Gardner, Mark | Mongan, Ann | Omilian, Angela R. | Conroy, Jeff | Bshara, Wiam | Angela, Omilian | Burgher, Blake | Ji, He | Glenn, Sean | Morrison, Carl | Mongan, Ann | Obeid, Joseph M. | Erdag, Gulsun | Smolkin, Mark E. | Deacon, Donna H. | Patterson, James W. | Chen, Lieping | Bullock, Timothy N. | Slingluff, Craig L. | Obeid, Joseph M. | Erdag, Gulsun | Deacon, Donna H. | Slingluff, Craig L. | Bullock, Timothy N. | Loffredo, John T. | Vuyyuru, Raja | Beyer, Sophie | Spires, Vanessa M. | Fox, Maxine | Ehrmann, Jon M. | Taylor, Katrina A. | Korman, Alan J. | Graziano, Robert F. | Page, David | Sanchez, Katherine | Ballesteros-Merino, Carmen | Martel, Maritza | Bifulco, Carlo | Urba, Walter | Fox, Bernard | Patel, Sapna P. | De Macedo, Mariana Petaccia | Qin, Yong | Reuben, Alex | Spencer, Christine | Guindani, Michele | Bassett, Roland | Wargo, Jennifer | Racolta, Adriana | Kelly, Brian | Jones, Tobin | Polaske, Nathan | Theiss, Noah | Robida, Mark | Meridew, Jeffrey | Habensus, Iva | Zhang, Liping | Pestic-Dragovich, Lidija | Tang, Lei | Sullivan, Ryan J. | Logan, Theodore | Khushalani, Nikhil | Margolin, Kim | Koon, Henry | Olencki, Thomas | Hutson, Thomas | Curti, Brendan | Roder, Joanna | Blackmon, Shauna | Roder, Heinrich | Stewart, John | Amin, Asim | Ernstoff, Marc S. | Clark, Joseph I. | Atkins, Michael B. | Kaufman, Howard L. | Sosman, Jeffrey | Weber, Jeffrey | McDermott, David F. | Weber, Jeffrey | Kluger, Harriet | Halaban, Ruth | Snzol, Mario | Roder, Heinrich | Roder, Joanna | Asmellash, Senait | Steingrimsson, Arni | Blackmon, Shauna | Sullivan, Ryan J. | Wang, Chichung | Roman, Kristin | Clement, Amanda | Downing, Sean | Hoyt, Clifford | Harder, Nathalie | Schmidt, Guenter | Schoenmeyer, Ralf | Brieu, Nicolas | Yigitsoy, Mehmet | Madonna, Gabriele | Botti, Gerardo | Grimaldi, Antonio | Ascierto, Paolo A. | Huss, Ralf | Athelogou, Maria | Hessel, Harald | Harder, Nathalie | Buchner, Alexander | Schmidt, Guenter | Stief, Christian | Huss, Ralf | Binnig, Gerd | Kirchner, Thomas | Sellappan, Shankar | Thyparambil, Sheeno | Schwartz, Sarit | Cecchi, Fabiola | Nguyen, Andrew | Vaske, Charles | Hembrough, Todd
Journal for Immunotherapy of Cancer  2016;4(Suppl 1):1-106.
doi:10.1186/s40425-016-0172-7
PMCID: PMC5123387
12.  Intrathecal administration of tumor-infiltrating lymphocytes is well tolerated in a patient with leptomeningeal disease from metastatic melanoma: A case report 
Cancer immunology research  2015;3(11):1201-1206.
Patients with leptomeningeal disease (LMD) from melanoma have very poor outcomes and few treatment options. We present a case of intrathecal (IT) administration of autologous tumor infiltrating lymphocytes (TIL) in a patient with LMD from metastatic melanoma. The patient developed LMD after previous treatments with surgery, high-dose bolus interleukin-2 (HD IL-2), and systemic TIL infusion and experienced radiographic progression after intrathecal IL2 (IT IL-2) therapy. The patient received weekly treatment with increasing numbers of IT TIL followed by twice-weekly IT IL-2. The patient received three IT TIL infusions and did not experience any toxicities beyond those expected with IT IL-2 therapy. Analysis of cerebrospinal fluid (CSF) demonstrated increased inflammatory cytokines following the intrathecal treatments. Subsequent imaging demonstrated disease stabilization, and neurological deficits also remained stable. The patient expired five months after the initiation of IT TIL therapy with disease progression in the brain, liver, lung, and peritoneal and retroperitoneal lymph nodes, but without LMD progression. These results demonstrate the safety of intrathecal administration of TIL in melanoma patients with LMD and support the feasibility of conducting a prospective clinical trial to determine this therapy's clinical benefit among these patients.
doi:10.1158/2326-6066.CIR-15-0071
PMCID: PMC4861225  PMID: 26216417
13.  Novel algorithmic approach predicts tumor mutation load and correlates with immunotherapy clinical outcomes using a defined gene mutation set 
BMC Medicine  2016;14:168.
Background
While clinical outcomes following immunotherapy have shown an association with tumor mutation load using whole exome sequencing (WES), its clinical applicability is currently limited by cost and bioinformatics requirements.
Methods
We developed a method to accurately derive the predicted total mutation load (PTML) within individual tumors from a small set of genes that can be used in clinical next generation sequencing (NGS) panels. PTML was derived from the actual total mutation load (ATML) of 575 distinct melanoma and lung cancer samples and validated using independent melanoma (n = 312) and lung cancer (n = 217) cohorts. The correlation of PTML status with clinical outcome, following distinct immunotherapies, was assessed using the Kaplan–Meier method.
Results
PTML (derived from 170 genes) was highly correlated with ATML in cutaneous melanoma and lung adenocarcinoma validation cohorts (R2 = 0.73 and R2 = 0.82, respectively). PTML was strongly associated with clinical outcome to ipilimumab (anti-CTLA-4, three cohorts) and adoptive T-cell therapy (1 cohort) clinical outcome in melanoma. Clinical benefit from pembrolizumab (anti-PD-1) in lung cancer was also shown to significantly correlate with PTML status (log rank P value < 0.05 in all cohorts).
Conclusions
The approach of using small NGS gene panels, already applied to guide employment of targeted therapies, may have utility in the personalized use of immunotherapy in cancer.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-016-0705-4) contains supplementary material, which is available to authorized users.
doi:10.1186/s12916-016-0705-4
PMCID: PMC5078889  PMID: 27776519
Melanoma; Lung cancer; Total mutation load; CTLA-4; PD-1; Immunotherapy
14.  A case report of Grover’s disease from immunotherapy-a skin toxicity induced by inhibition of CTLA-4 but not PD-1 
Background
Immune related adverse events (irAEs) are common side effects of checkpoint inhibitory (CPI) therapies targeting CTLA-4 and PD-1/PD-L1. Grover’s disease is an uncommon dermatologic condition with unclear pathogenesis previously reported as an irAE with ipilimumab.
Case Presentation
We report an additional case of ipilimumab-induced Grover’s disease. Interestingly, this dermatologic side effect did not appear with use of anti-PD-1 therapy in our patient. Immune analysis was performed and suggests a possible role of Th2 cells in its patholgenesis.
Conclusion
This case suggests that Grover's disease is an irAE induced by Ipilimumab. Our immune analysis suggests that Th2 cells may be pathogenic mediators which warrants further study.
doi:10.1186/s40425-016-0157-6
PMCID: PMC5028978  PMID: 27660709
15.  Selective inhibition of autoimmune exacerbation while preserving the anti-tumor clinical benefit using IL-6 blockade in a patient with advanced melanoma and Crohn’s disease: a case report 
Background
Novel immunotherapies, or checkpoint inhibitors, targeting programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) have significantly improved outcomes for patients with numerous different cancer types. However, owing to their exclusion from clinical trials and risk for autoimmune exacerbation on these treatments, the impact on safety and degree of toxicity of these potentially life-prolonging therapies is not well characterized in patients with an underlying autoimmune disease or previous organ transplant.
Case presentation
We report a case of a patient with advanced melanoma and refractory Crohn’s disease who was treated concurrently with pembrolizumab (anti-PD-1 antibody) and tocilizumab (anti-interluekin-6 receptor antibody). This novel treatment strategy was well tolerated and did not result in Crohn’s disease exacerbation for at least 16 weeks. Importantly, this treatment resulted in marked, durable antitumor responses.
Conclusions
This outcome suggests that targeted immunosuppression combined with checkpoint inhibitors may hold promise as a treatment strategy for this unique patient population and may warrant additional study.
doi:10.1186/s13045-016-0309-7
PMCID: PMC5011857  PMID: 27595932
Checkpoint inhibitors; PD-1; CTLA-4; Pembrolizumab; Tocilizumab; Crohn’s disease; Metastatic melanoma
16.  Loss of PTEN promotes resistance to T cell-mediated immunotherapy 
Cancer discovery  2015;6(2):202-216.
T cell-mediated immunotherapies are promising cancer treatments. However, most patients still fail to respond to these therapies. The molecular determinants of immune resistance are poorly understood. We show that loss of PTEN in tumor cells in preclinical models of melanoma inhibits T cell-mediated tumor killing and decreases T cell trafficking into tumors. In patients, PTEN loss correlates with decreased T cell infiltration at tumor sites, reduced likelihood of successful T cell expansion from resected tumors, and inferior outcomes with PD-1 inhibitor therapy. PTEN loss in tumor cells increased the expression of immunosuppressive cytokines, resulting in decreased T cell infiltration in tumors, and inhibited autophagy, which decreased T cell-mediated cell death. Treatment with a selective PI3Kβ inhibitor improved the efficacy of both anti-PD-1 and anti-CTLA4 antibodies in murine models. Together these findings demonstrate that PTEN loss promotes immune resistance and support the rationale to explore combinations of immunotherapies and PI3K-AKT pathway inhibitors.
doi:10.1158/2159-8290.CD-15-0283
PMCID: PMC4744499  PMID: 26645196
PTEN loss; Immunotherapy
17.  Immune-Modulation by Epidermal Growth Factor Receptor Inhibitors: Implication on Anti-Tumor Immunity in Lung Cancer 
PLoS ONE  2016;11(7):e0160004.
Skin toxicity is the most common toxicity caused by Epidermal Growth Factor Receptor (EGFR) inhibitors, and has been associated with clinical efficacy. As EGFR inhibitors enhance the expression of antigen presenting molecules in affected skin keratinocytes, they may concurrently facilitate neo-antigen presentation in lung cancer tumor cells contributing to anti-tumor immunity. Here, we investigated the modulatory effect of the EGFR inhibitor, erlotinib on antigen presenting molecules and PD-L1, prominent immune checkpoint protein, of skin keratinocytes and lung cancer cell lines to delineate the link between EGFR signaling pathway inhibition and potential anti-tumor immunity. Erlotinib up-regulated MHC-I and MHC-II proteins on IFNγ treated keratinocytes but abrogated IFNγ-induced expression of PD-L1, suggesting the potential role of infiltrating autoreactive T cells in the damage of keratinocytes in affected skin. Interestingly, the surface expression of MHC-I, MHC-II, and PD-L1 was up-regulated in response to IFNγ more often in lung cancer cell lines sensitive to erlotinib, but only expression of PD-L1 was inhibited by erlotinib. Further, erlotinib significantly increased T cell mediated cytotoxicity on lung cancer cells. Lastly, the analysis of gene expression dataset of 186 lung cancer cell lines from Cancer Cell Line Encyclopedia demonstrated that overexpression of PD-L1 was associated with sensitivity to erlotinib and higher expression of genes related to antigen presenting pathways and IFNγ signaling pathway. Our findings suggest that the EGFR inhibitors can facilitate anti-tumor adaptive immune responses by breaking tolerance especially in EGFR driven lung cancer that are associated with overexpression of PD-L1 and genes related to antigen presentation and inflammation.
doi:10.1371/journal.pone.0160004
PMCID: PMC4965069  PMID: 27467256
18.  BRAF(V600E) co-opts a conserved MHC class I internalization pathway to diminish antigen presentation and CD8+ T-cell recognition of melanoma 
Cancer immunology research  2015;3(6):602-609.
Oncogene activation in tumor cells induces broad and complex cellular changes that contribute significantly to disease initiation and progression. In melanoma, oncogenic BRAF(V600E) has been shown to drive the transcription of a specific gene signature that can promote multiple mechanisms of immune suppression within the tumor microenvironment. We show here that BRAF(V600E) also induces rapid internalization of MHC class I (MHC-I) from the melanoma cell surface and its intracellular sequestration within endolysosomal compartments. Importantly, MAP kinase inhibitor treatment quickly restored MHC-I surface expression in tumor cells, thereby enhancing melanoma antigen-specific T-cell recognition and effector function. MAP kinase pathway-driven re-localization of HLA-A*0201 required a highly conserved cytoplasmic serine phosphorylation site previously implicated in rapid MHC-I internalization and recycling by activated immune cells. Collectively, these data suggest that oncogenic activation of BRAF allows tumor cells to co-opt an evolutionarily conserved MHC-I trafficking pathway as a strategy to facilitate immune evasion. This link between MAPK pathway activation and the MHC-I cytoplasmic tail has direct implications for immunologic recognition of tumor cells, and provides further evidence to support testing therapeutic strategies combining MAP kinase pathway inhibition with immunotherapies in the clinical setting.
doi:10.1158/2326-6066.CIR-15-0030
PMCID: PMC4457616  PMID: 25795007
Cancer; melanoma; oncogene; BRAF(V600E); MAP kinase pathway; MHC class I; HLA; cytotoxic T lymphocytes (CTL); immunotherapy; targeted therapy; MAPK inhibition
19.  BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties 
Oncoimmunology  2015;4(8):e1014246.
In a recent adoptive cell therapy (ACT) clinical trial using autologous tumor-infiltrating lymphocytes (TILs) in patients with metastatic melanoma, we found an association between CD8+ T cells expressing the inhibitory receptor B- and T-lymphocyte attenuator (BTLA) and clinical response. Here, we further characterized this CD8+BTLA+ TIL subset and their CD8+BTLA− counterparts. We found that the CD8+ BTLA+ TILs had an increased response to IL-2, were less-differentiated effector-memory (TEM) cells, and persisted longer in vivo after infusion. In contrast, CD8+BTLA− TILs failed to proliferate and expressed genes associated with T-cell deletion/tolerance. Paradoxically, activation of BTLA signaling by its ligand, herpes virus entry mediator (HVEM), inhibited T-cell division and cytokine production, but also activated the Akt/PKB pathway thus protecting CD8+BTLA+ TILs from apoptosis. Our results point to a new role of BTLA as a useful T-cell differentiation marker in ACT and a dual signaling molecule that curtails T-cell activation while also conferring a survival advantage for CD8+ T cells. These attributes may explain our previous observation that BTLA expression on CD8+ TILs correlates with clinical response to adoptive T-cell therapy in metastatic melanoma.
doi:10.1080/2162402X.2015.1014246
PMCID: PMC4570103  PMID: 26405566
B- and T-lymphocyte attenuator; CD8+ effector-memory; melanoma; T cell survival/persistence; tumor-infiltrating lymphocytes

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