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PubMed Central Canada to be taken offline in February 2018

On February 23, 2018, PubMed Central Canada (PMC Canada) will be taken offline permanently. No author manuscripts will be deleted, and the approximately 2,900 manuscripts authored by Canadian Institutes of Health Research (CIHR)-funded researchers currently in the archive will be copied to the National Research Council’s (NRC) Digital Repository over the coming months. These manuscripts along with all other content will also remain publicly searchable on PubMed Central (US) and Europe PubMed Central, meaning such manuscripts will continue to be compliant with the Tri-Agency Open Access Policy on Publications.

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author:("Li, fanyun")
1.  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
2.  Synergistic mechanism of Ag+–Zn2+ in anti-bacterial activity against Enterococcus faecalis and its application against dentin infection 
Background
Ag+ and Zn2+ have already been used in combinations to obtain both enhanced antibacterial effect and low cytotoxicity. Despite this, it is still unclear how the Zn2+ co-works with Ag+ in the synergistic antibacterial activity. The main purposes of this study were to investigate the co-work pattern and optimum ratio between Ag+ and Zn2+ in their synergistic antibacterial activity against E. faecalis, the possible mechanisms behind this synergy and the primary application of optimum Ag+–Zn2+ co-work pattern against the E. faecalis biofilm on dentin. A serial of Ag+–Zn2+ atomic combination ratios were tested on both planktonic and biofilm-resident E. faecalis on dentin, their antibacterial efficiency was calculated and optimum ratio determined. And the cytotoxicity of various Ag+–Zn2+ atomic ratios was tested on MC3T3-E1 Cells. The role of Zn2+ in Ag+–Zn2+co-work was evaluated using a Zn2+ pretreatment study and membrane potential—permeability measurement.
Results
The results showed that the synergistically promoted antibacterial effect of Ag+–Zn2+ combinations was Zn2+ amount-dependent with the 1:9 and 1:12 Ag+–Zn2+ atomic ratios showing the most powerful ability against both planktonic and biofilm-resident E. faecalis. This co-work could likely be attributed to the depolarization of E. faecalis cell membrane by the addition of Zn2+. The cytotoxicity of the Ag+–Zn2+ atomic ratios of 1:9 and 1:12 was much lower than 2% chlorhexidine.
Conclusions
The Ag+–Zn2+ atomic ratios of 1:9 and 1:12 demonstrated similar strong ability against E. faecalis biofilm on dentin but much lower cytotoxicity than 2% chlorhexidine. New medications containing optimum Ag+–Zn2+ atomic ratios higher than 1:6, such as 1:9 or 1:12, could be developed against E. faecalis infection in root canals of teeth or any other parts of human body.
doi:10.1186/s12951-018-0336-3
PMCID: PMC5793365  PMID: 29386060
Silver; Zinc; Ion; Antibacterial; Biofilm; Dentin; E. faecalis
3.  Contribution of birth weight and adult waist circumference to cardiovascular disease risk in a longitudinal study 
Scientific Reports  2017;7:9768.
To determine the association of birth weight (BW) and waist circumference (WC) on cardiovascular disease (CVD). The longitudinal cohort study consisted of 745 participants who were able to provide their birth weight information and were followed from 2002 to 2014. During the follow-up, 83 events of CVD were confirmed. After adjusting for confounding factors, subjects with birth weight <2500 g were at a significantly increased CVD risk when compared to subjects with birth weight between 2500–3999 g (OR 2·47, 95%CI, 1·07–5·71). When high waist circumference (HWC), a measurement of adult obesity, was incorporated into stratifying factors according to presence or absence of low birth weight (LBW, birth weight <2500 g), adjusted CVD risk was significantly elevated in -LBW/+ HWC group (OR 1·94, 95%CI, 1·10–3·43) and marginally significantly increased in +LBW/-HWC group (OR 2·94, 95%CI, 1·00–8·64). CVD risk was highest in subjects with LBW and HWC (+LBW/+HWC), OR 4·74 (95%CI, 1·48–15·21). Higher waist circumference in adulthood is an especially strong risk factor for cardiovascular disease among those small at birth. In this cohort, birth size and adiposity in adulthood interact to predict events of cardiovascular disease.
doi:10.1038/s41598-017-10176-6
PMCID: PMC5575020  PMID: 28852140
4.  Heterogeneous Tumor-Immune Microenvironments among Differentially Growing Metastases in an Ovarian Cancer Patient 
Cell  2017;170(5):927-938.e20.
Summary
We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8+ and CD4+ T cells and exhibited oligoclonal expansion of specific T cell subsets. We also detected CD8+ T cell reactivity against predicted neoepitopes after isolation of cells from a blood sample taken almost 3 years after the tumors were resected. These findings suggest that multiple distinct tumor immune microenvironments co-exist within a single individual and may explain in part the heterogeneous fates of metastatic lesions often observed in the clinic post-therapy.
Video Abstract
Graphical Abstract
Highlights
•Differential progression of metastases during off-treatment period.•Coexistence of distinct tumor-immune microenvironments within the same individual.•Tumor regression and progression correlated with T cell infiltration and exclusion.•Clonal neoepitopes elicited reactivity of circulating CD8+ T cells.
Distinct tumor immune microenvironments co-exist within a single individual and may help to explain the heterogeneous fates of metastatic lesions often observed post-therapy.
doi:10.1016/j.cell.2017.07.025
PMCID: PMC5589211  PMID: 28841418
5.  Closer to a Uniform Language in Colposcopy: Study on the Potential Application of 2011 International Federation for Cervical Pathology and Colposcopy Terminology in Clinical Practice 
BioMed Research International  2017;2017:8984516.
As the newest colposcopic terminology, the 2011 International Federation for Cervical Pathology and Colposcopy (IFCPC) classification provides standardized interpretation of colposcopic findings. In this study, we analyzed the colposcopic accuracy and the significance of individual findings according to the 2011 IFCPC classification in 525 patients, reviewed by 13 trained colposcopists. Results show that colposcopic diagnoses are in 64.95% perfect agreement with cervical pathology, with 63.64% sensitivity and 96.01% specificity for high-grade squamous intraepithelial lesion (HSIL+). And the accuracy is reproducible across different experienced examiners. Many individual findings, especially the two new signs, inner border sign and ridge sign, are proved to have good predictive accuracy, while iodine negativity demonstrates an inferior performance. However, the distribution of three cervical transformation zone (TZ) types is heterogeneous in examiners. A comparison was also made of the findings of another two colposcopists without nomenclature training according to the Reid Colposcopic Index (RCI), modified RCI, and Swede Score. Results show that colposcopic accuracies in them are lower than in those nomenclature trained colposcopists. The 2011 IFCPC nomenclature improves colposcopic accuracy in trained colposcopists, like speaking the same language. However, the reproducibility of TZ and the predictive value of a few signs remain to be discussed.
doi:10.1155/2017/8984516
PMCID: PMC5463115
6.  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. 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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
7.  Calcium-silicate mesoporous nanoparticles loaded with chlorhexidine for both anti- Enterococcus faecalis and mineralization properties 
Background
In infected periapical tissues, Enterococcus faecalis is one of the most common dominant bacteria. Chlorhexidine has been proved to show strong antibacterial ability against E. faecalis but is ineffective in promoting mineralization for tissues around root apex. Mesoporous calcium-silicate nanoparticles are newly synthesized biomaterials with excellent ability to promote mineralization and carry-release bioactive molecules in a controlled manner. In this study, mesoporous calcium-silicate nanoparticles were functionalized with chlorhexidine and their releasing profile, antibacterial ability, effect on cell proliferation and in vitro mineralization property were evaluated.
Results
The chlorhexidine was successfully incorporated into mesoporous calcium-silicate nanoparticles by a mixing-coupling method. The new material could release chlorhexidine as well as Ca2+ and SiO3 2− in a sustained manner with an alkaline pH value under different conditions. The antimicrobial ability against planktonic E. faecalis was dramatically improved after chlorhexidine incorporation. The nanoparticles with chlorhexidine showed no negative effect on cell proliferation with low concentrations. On dentin slices, the new synthesized material demonstrated a similar inhibitory effect on E. faecalis as the chlorhexidine. After being immersed in SBF for 9 days, numerous apatite crystals could be observed on surfaces of the material tablets.
Conclusions
Mesoporous calcium-silicate nanoparticles loaded with chlorhexidine exhibited release of ions and chlorhexidine, low cytotoxicity, excellent antibacterial ability and in vitro mineralization. This material could be developed into a new effective intra-canal medication in dentistry or a new bone defect filling material for infected bone defects.
doi:10.1186/s12951-016-0224-7
PMCID: PMC5073856  PMID: 27769275
Mesoporous; Nanoparticle; Enterococcus faecalis; Chlorhexidine; Mineralization
8.  Tumor-expressed IDO recruits and activates MDSCs in a Treg-dependent manner 
Cell reports  2015;13(2):412-424.
Indoleamine 2,3-dioxygenase (IDO) has been described as a major mechanism of immunosuppression in tumors, though the mechanisms of this are poorly understood. Here, we find that expression of IDO by tumor cells results in aggressive tumor growth and resistance to T-cell targeting immunotherapies. We demonstrate that IDO orchestrates local and systemic immunosuppressive effects through recruitment and activation of myeloid-derived suppressor cells (MDSCs), through a mechanism dependent on regulatory T cells (Tregs). Supporting these findings, we find that IDO expression in human melanoma tumors is strongly associated with MDSC infiltration. Treatment with a selective IDO inhibitor in vivo reversed tumor-associated immunosuppression by decreasing numbers of tumor-infiltrating MDSCs and Tregs, and abolishing their suppressive function. These findings establish an important link between IDO and multiple immunosuppressive mechanisms active in the tumor microenvironment, providing a strong rationale for therapeutic targeting IDO as one of the central regulators of immune suppression.
eTOC BLURB
IDO mediates immune inhibition in tumors, though the mechanisms of this are poorly understood. Holmgaard et al. demonstrate that tumor IDO is a central regulator of both local and systemic immunosuppression and resistance to immunotherapy, which is orchestrated through expansion, recruitment, and activation of MDSCs in a Treg-dependent manner.
doi:10.1016/j.celrep.2015.08.077
PMCID: PMC5013825  PMID: 26411680
9.  MiR-202 promotes endometriosis by regulating SOX6 expression 
Objectives: This study is to investigate the role and mechanism of microRNA-202 (miR-202) in endometriosis. Methods: Forty-five cases of ectopic endometrial tissues, 25 cases of eutopic endometrial tissues and 26 cases of normal endometrial tissues were collected. MiR-202 expression was detected by quantitative RT-PCR. The protein expressions of SOX6 (sex determining region Y-box 6) and its downstream proteins (p21, cyclin D1 and pRb (retinoblastoma protein)) were detected by immunochemistry and western blot. MTT and transwell assays were used to examine cell proliferation and cell migration. The dual luciferase assay was applied to validate whether miR-202 can directly target SOX6 gene. Results: MiR-202 was highly expressed in eutopic and ectopic endometrial tissues than normal endometrial tissues (P < 0.05), and the expression was higher in tissues with III/IV stages than I/II stages (P < 0.05). The expression of SOX6 protein was lower in ectopic endometrial tissues than in normal endometrial tissues. In ectopic endometrial tissues, the expression of p21 was decreased while cyclin D1 and pRb was up-regulated than in normal endometrial tissues (P < 0.05). In cultured endometrial cells, miR-202 down-regulation induced up-regulation of SOX6 and p21 whereas down-regulation of cyclin D1 and pRb. MiR-202 promoted the proliferation and metastasis of endometrial cells. And, miR-202 could complementary bind to SOX6 3’UTR to regulate the expression of SOX6. Conclusion: MiR-202 was up-regulated in the endometriosis. Through targeting SOX6 and its downstream proteins (p21, cyclin D1 and pRb), miR-202 can promote the progression of endometriosis.
PMCID: PMC4694266  PMID: 26770366
EMs; miR-202; SOX6
10.  TNF Induction of NF-κB RelB Enhances RANKL-Induced Osteoclastogenesis by Promoting Inflammatory Macrophage Differentiation but also Limits It through Suppression of NFATc1 Expression 
PLoS ONE  2015;10(8):e0135728.
TNF induces bone loss in common bone diseases by promoting osteoclast formation directly and indirectly, but it also limits osteoclast formation by inducing expression of NF-κB p100. Osteoclast precursors (OCPs) are derived from M1 (inflammatory) and M2 (resident) macrophages. However, it is not known if TNF stimulates or limits osteoclast formation through regulation of M1 or M2 differentiation or if RelB, a partner of p100, is involved. To investigate these questions, we treated bone marrow cells (BMCs) with M-CSF alone or in combination with TNF to enrich for OCPs, which we called M-OCPs and T-OCPs, respectively. We found that TNF switched CD11b+F4/80+ M-OCPs from Ly6C-Gr1- M2 to Ly6C+Gr1-CD11c+ and Ly6C-Gr1-CD11c+ M1 cells. RANKL induced osteoclast formation from both Ly6C+Gr1- and Ly6C-Gr1- T-OCPs, but only from Ly6C+Gr1- M-OCPs, which formed significantly fewer osteoclasts than T-OCPs. Importantly, Ly6C+Gr1- cells from both M- and T-OCPs have increased expression of the M1 marker genes, iNOS, TNF, IL-1β and TGFβ1, compared to Ly6C-Gr1- cells, and Ly6C-Gr1- cells from T-OCPs also have increased expression of iNOS and TGFβ1 compared to cells from M-OCPs. Both RANKL and TNF increased RelB mRNA expression. TNF significantly increased RelB protein levels, but RANKL did not because it also induced RelB proteasomal degradation. TNF inhibited RANKL-induced NFATc1 mRNA expression and osteoclast formation from M-OCPs, but not from T-OCPs, and it did not induce Ly6C+Gr1-CD11c+ or Ly6C-Gr1-CD11c+ M1 macrophages from RelB-/- BMCs. Furthermore, overexpression of RelB in M-OCPs reduced RANKL-induced osteoclast formation and NFATc1 mRNA expression, but it increased TNF-induced OC formation without affecting NFATc1 levels. Thus, TNF induction of RelB directly mediates terminal osteoclast differentiation independent of NFATc1 and limits RANKL-induced osteoclastogenesis by inhibiting NFATc1 activation. However, the dominant role of TNF is to expand the OCP pool by switching the differentiation of M-CSF-induced M2 to M1 macrophages with enhanced osteoclast forming potential. Strategies to degrade RelB could prevent TNF-induced M2/M1 switching and reduce osteoclast formation.
doi:10.1371/journal.pone.0135728
PMCID: PMC4545392  PMID: 26287732
11.  Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma 
The New England journal of medicine  2014;371(23):2189-2199.
BACKGROUND
Immune checkpoint inhibitors are effective cancer treatments, but molecular determinants of clinical benefit are unknown. Ipilimumab and tremelimumab are antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4). Anti–CTLA-4 treatment prolongs overall survival in patients with melanoma. CTLA-4 blockade activates T cells and enables them to destroy tumor cells.
METHODS
We obtained tumor tissue from patients with melanoma who were treated with ipilimumab or tremelimumab. Whole-exome sequencing was performed on tumors and matched blood samples. Somatic mutations and candidate neoantigens generated from these mutations were characterized. Neoantigen peptides were tested for the ability to activate lymphocytes from ipilimumab-treated patients.
RESULTS
Malignant melanoma exomes from 64 patients treated with CTLA-4 blockade were characterized with the use of massively parallel sequencing. A discovery set consisted of 11 patients who derived a long-term clinical benefit and 14 patients who derived a minimal benefit or no benefit. Mutational load was associated with the degree of clinical benefit (P = 0.01) but alone was not sufficient to predict benefit. Using genomewide somatic neoepitope analysis and patient-specific HLA typing, we identified candidate tumor neoantigens for each patient. We elucidated a neo-antigen landscape that is specifically present in tumors with a strong response to CTLA-4 blockade. We validated this signature in a second set of 39 patients with melanoma who were treated with anti–CTLA-4 antibodies. Predicted neoantigens activated T cells from the patients treated with ipilimumab.
CONCLUSIONS
These findings define a genetic basis for benefit from CTLA-4 blockade in melanoma and provide a rationale for examining exomes of patients for whom anti–CTLA-4 agents are being considered. (Funded by the Frederick Adler Fund and others.)
doi:10.1056/NEJMoa1406498
PMCID: PMC4315319  PMID: 25409260
12.  Two less common human microRNAs miR-875 and miR-3144 target a conserved site of E6 oncogene in most high-risk human papillomavirus subtypes 
Protein & Cell  2015;6(8):575-588.
Human papillomaviruses (HPVs) including high-risk (HR) and low-risk (LR) subtypes have distinguishable variation on both genotypes and phenotypes. The co-infection of multiple HR-HPVs, headed by HPV16, is common in cervical cancer in female. Recently accumulating reports have focused on the interaction between virus and host, particularly the role of human microRNAs (miRNAs) in anti-viral defense by targeting viral genome. Here, we found a well-conserved target site of miRNAs in the genomes of most HR-HPVs, not LR-HPVs, by scanning all potential target sites of human miRNAs on 24 HPVs of unambiguous subtypes of risk. The site is targeted by two less common human miRNAs, miR-875 and miR-3144, and is located in E6 oncogene open reading frame (ORF) and overlap with the first alternative splice exon of viral early transcripts. In validation tests, miR-875 and miR-3144 were identified to suppress the target reporter activity markedly and inhibit the expression of both synthetically exogenous E6 and endogenous E6 oncogene. High level of two miRNAs can inhibit cell growth and promote apoptosis in HPV16-positive cervical cancer cells. This study provides a promising common target of miRNAs for most HR-HPVs and highlights the effects of two low expressed human miRNAs on tumour suppression.
doi:10.1007/s13238-015-0142-8
PMCID: PMC4506288  PMID: 25913515
human papillomavirus; microRNA; E6; miR-875; miR-3144
13.  Two less common human microRNAs miR-875 and miR-3144 target a conserved site of E6 oncogene in most high-risk human papillomavirus subtypes 
Protein & Cell  2015;6(8):575-588.
Human papillomaviruses (HPVs) including high-risk (HR) and low-risk (LR) subtypes have distinguishable variation on both genotypes and phenotypes. The co-infection of multiple HR-HPVs, headed by HPV16, is common in cervical cancer in female. Recently accumulating reports have focused on the interaction between virus and host, particularly the role of human microRNAs (miRNAs) in anti-viral defense by targeting viral genome. Here, we found a well-conserved target site of miRNAs in the genomes of most HR-HPVs, not LR-HPVs, by scanning all potential target sites of human miRNAs on 24 HPVs of unambiguous subtypes of risk. The site is targeted by two less common human miRNAs, miR-875 and miR-3144, and is located in E6 oncogene open reading frame (ORF) and overlap with the first alternative splice exon of viral early transcripts. In validation tests, miR-875 and miR-3144 were identified to suppress the target reporter activity markedly and inhibit the expression of both synthetically exogenous E6 and endogenous E6 oncogene. High level of two miRNAs can inhibit cell growth and promote apoptosis in HPV16-positive cervical cancer cells. This study provides a promising common target of miRNAs for most HR-HPVs and highlights the effects of two low expressed human miRNAs on tumour suppression.
doi:10.1007/s13238-015-0142-8
PMCID: PMC4506288  PMID: 25913515
human papillomavirus; microRNA; E6; miR-875; miR-3144
14.  NF-κB RelB Negatively Regulates Osteoblast Differentiation and Bone Formation 
RelA-mediated NF-κB canonical signaling promotes mesenchymal progenitor cell (MPC) proliferation, but inhibits differentiation of mature osteoblasts (OBs) and thus negatively regulates bone formation. Previous studies suggest that NF-κB RelB may also negatively regulate bone formation through non-canonical signaling, but they involved a complex knockout mouse model and the molecular mechanisms involved were not investigated. Here, we report that RelB−/− mice develop age-related increased trabecular bone mass associated with increased bone formation. RelB−/− bone marrow stromal cells expanded faster in vitro and have enhanced OB differentiation associated with increased expression of the osteoblastogenic transcription factor, Runx2. In addition, RelB directly targeted the Runx2 promoter to inhibit its activation. Importantly, RelB−/− bone-derived MPCs formed bone more rapidly than wild-type cells after they were injected into a murine tibial bone defect model. Our findings indicate that RelB negatively regulates bone mass as mice age and limits bone formation in healing bone defects, suggesting that inhibition of RelB could reduce age-related bone loss and enhance bone repair.
doi:10.1002/jbmr.2108
PMCID: PMC3961566  PMID: 24115294
RelB; NF-κB; mesenchymal progenitor cells; osteoblasts; bone formation
15.  The Relationship between Serum 25-Hydroxy Vitamin D and Insulin Sensitivity and  β-Cell Function in Newly Diagnosed Type 2 Diabetes 
Journal of Diabetes Research  2015;2015:636891.
The aim of this study was to investigate the relationship between serum 25-hydroxy vitamin D (25-OHD) and insulin sensitivity and β-cell function in newly diagnosed type 2 diabetes. 395 newly diagnosed type 2 diabetes patients were enrolled in this study. Venous blood samples were collected at 0 min, 30 min, and 120 min of OGTT to measure serum glucose and insulin. Matsuda ISI and HOMA-IR were used to determine insulin sensitivity. The ratio of 0–120 min area under curve of insulin to glucose (insulin release index, INSR) was calculated as surrogate index of β-cell insulin secretion function. The products of insulin secretion indices multiplied by Matsuda insulin sensitivity index were used as disposition indices. Patients were divided into three groups according to tertiles (T1, T2, and T3) of 25-OHD concentration. There was significant difference among three groups for HOMA-IR, Matsuda ISI, and INSR. HOMA-IR, Matsuda ISI, INSR, and DI were undifferentiated among three groups in male patients. But HOMA-IR, Matsuda ISI, and INSR were significantly different among three groups in female patients after being adjusted by confounding factors. In conclusion, serum 25-OHD is associated with insulin sensitivity and β-cell function for female newly diagnosed type 2 diabetes patients, and the association is ambiguous in males.
doi:10.1155/2015/636891
PMCID: PMC4337093  PMID: 25741510
16.  Association of High Vitamin D Status with Low Circulating Thyroid-Stimulating Hormone Independent of Thyroid Hormone Levels in Middle-Aged and Elderly Males 
Background. A recent study has reported that high circulating 25-hydroxyvitamin D [25(OH)D] is associated with low circulating thyroid-stimulating hormone (TSH) levels, but only in younger individuals. The goal of the present study was to explore the relationship between vitamin D status and circulating TSH levels with thyroid autoimmunity and thyroid hormone levels taken into consideration in a population-based health survey of middle-aged and elderly individuals. Methods. A total of 1,424 Chinese adults, aged 41–78 years, were enrolled in this cross-sectional study. Serum levels of 25(OH)D, TSH, thyroid hormones, and thyroid autoantibodies were measured. Results. The prevalence of vitamin D insufficiency was 94.29% in males and 97.22% in females, and the prevalence of vitamin D deficiency was 55.61% in males and 69.64% in females. Vitamin D status was not associated with positive thyroid autoantibodies after controlling for age, gender, body mass index, and smoking status. Higher 25(OH)D levels were associated with lower TSH levels after controlling for age, FT4 and FT3 levels, thyroid volume, the presence of thyroid nodule(s), and smoking status in males. Conclusion. High vitamin D status in middle-aged and elderly males was associated with low circulating TSH levels independent of thyroid hormone levels.
doi:10.1155/2014/631819
PMCID: PMC3947886  PMID: 24693286
17.  Combining glycosylated hemoglobin A1c and fasting plasma glucose for diagnosis of type 2 diabetes in Chinese adults 
Background
Glycosylated hemoglobin A1c (HbA1c) has been applied to identify type 2 diabetes (T2DM) in the U.S. and European countries. It has not been used in China mainly due to lack of a standardized approach to measure HbA1c, short of knowledge about racial-specific standard and deficiency of an optimal cut-off point.
Methods
To evaluate combination of HbA1c and fasting plasma glucose (FPG) in diagnosing T2DM in Chinese adults, a multistage sampling cross-sectional study was conducted in Shanghai, China, in 2009. The FPG measurement, HbA1c assay, and oral glucose tolerance test (OGTT) were performed in 6,661 Chinese adults (3057 men, 3604 women) who had no prior history of diabetes to identify the unrecognized T2DM.
Results
A total of 454 participants were identified as T2DM based on the 1999 World Health Organization (WHO) diagnostic criteria. Of these patients, 239 were detected using an FPG ≥ 7.0 mmol/l and 141 were further identified using an HbA1c ≥ 43 mmol/mol (6.1%), achieving a sensitivity of 83.7% and a specificity of 89.3% for combining use of FPG and HbA1c. In subjects at high risk of diabetes, the combining use of FPG and HbA1c produced a higher sensitivity and an improved positive predictive value (PPV), and had a satisfactory specificity and negative predictive value (NPV).
Conclusions
The combining use of FPG and HbA1c is a potential screening and diagnosis approach for T2DM in Chinese adults, especially among those at high risk of the disease.
doi:10.1186/1472-6823-13-44
PMCID: PMC3853138  PMID: 24099651
Type 2 diabetes; Diagnosis; Glycosylated hemoglobin A1c; Fasting plasma glucose; Chinese adults
18.  CTLA-4 blockade increases antigen-specific CD8+ T-cells in prevaccinated patients with melanoma: three cases 
Background
Anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibodies, such as ipilimumab, have generated measurable immune responses to Melan-A, NY-ESO-1, and gp100 antigens in metastatic melanoma. Vaccination against such targets has potential for immunogenicity and may produce an effector memory T-cell response.
Methods
To determine the effect of CTLA-4 blockade on antigen-specific responses following vaccination, in-depth immune monitoring was performed on three ipilimumab-treated patients prevaccinated with gp100 DNA (IMF-24), gp100209–217 and tyrosinase peptides plus GM-CSF DNA (IMF-32), or NY-ESO-1 protein plus imiquimod (IMF-11); peripheral blood mononuclear cells were analyzed by tetramer and/or intracellular cytokine staining following 10-day culture with HLA-A*0201-restricted gp100209–217 (ITDQVPFSV), tyrosinase369–377 (YMDGTMSQV), or 20-mer NY-ESO-1 overlapping peptides, respectively. Tumors from IMF-32 were analyzed by immunohistochemistry to help elucidate mechanism(s) underlying tumor escape.
Results
Following vaccination, patients generated weak to no CD4+ or CD8+ T-cell response specific to the vaccine antigen but demonstrated increases in effector memory (CCR7loCD45RAlo) tetramer+CD8+ T-cells. After ipilimumab induction, patients experienced a robust, although sometimes transient, antigen-specific response for gp100 (IMF-32 and IMF-24) or NY-ESO-1 (IMF-11) and produced polyfunctional intracellular cytokines. Primary and metastatic tumors expressed tyrosinase but not gp100 or class I/II MHC molecules.
Conclusion
Vaccination induced a measurable antigen-specific T-cell response which increased following CTLA-4 blockade, potentially “boosting” the vaccine-primed response. Tumor escape may be related to antigen loss or lack of MHC expression necessary for immune activity. These results in a limited number of patients support the need for further research into combining vaccination with ipilimumab and provide insight into mechanisms underlying tumor escape.
doi:10.1007/s00262-011-1011-9
PMCID: PMC3654853  PMID: 21465316
melanoma; cytotoxic T-lymphocyte antigen-4; ipilimumab; T-cell response; vaccines
19.  Induction of tumoricidal function in CD4+ T cells is associated with concomitant memory and terminally differentiated phenotype 
The Journal of Experimental Medicine  2012;209(11):2113-2126.
OX40 engagement induces a cytotoxic CD4+ T cell subpopulation to eradicate advance melanomas
Harnessing the adaptive immune response to treat malignancy is now a clinical reality. Several strategies are used to treat melanoma; however, very few result in a complete response. CD4+ T cells are important and potent mediators of anti-tumor immunity and adoptive transfer of specific CD4+ T cells can promote tumor regression in mice and patients. OX40, a costimulatory molecule expressed primarily on activated CD4+ T cells, promotes and enhances anti-tumor immunity with limited success on large tumors in mice. We show that OX40 engagement, in the context of chemotherapy-induced lymphopenia, induces a novel CD4+ T cell population characterized by the expression of the master regulator eomesodermin that leads to both terminal differentiation and central memory phenotype, with concomitant secretion of Th1 and Th2 cytokines. This subpopulation of CD4+ T cells eradicates very advanced melanomas in mice, and an analogous population of human tumor-specific CD4+ T cells can kill melanoma in an in vitro system. The potency of the therapy extends to support a bystander killing effect of antigen loss variants. Our results show that these uniquely programmed effector CD4+ T cells have a distinctive phenotype with increased tumoricidal capability and support the use of immune modulation in reprogramming the phenotype of CD4+ T cells.
doi:10.1084/jem.20120532
PMCID: PMC3478933  PMID: 23008334
20.  Relationship between the -455G/A and -148C/T polymorphisms in the beta-fibrinogen gene and cerebral infarction in the Xinjiang Uygur and Han Chinese populations☆ 
Neural Regeneration Research  2012;7(7):546-551.
We sought to investigate the correlation between the -455G/A and -148C/T polymorphisms of the β-fibrinogen gene and plasma fibrinogen levels in patients with cerebral infarction and in healthy subjects among the Xinjiang Uygur and Han Chinese populations, by using polymerase chain reaction-restriction enzyme digestion analysis. Results showed that there were no statistically significant differences in the distributions of the -455G/A genotype and allele frequency between the Uygurs and the Han. Plasma fibrinogen levels in cerebral infarction patients among the Uygurs and the Han were higher than those among healthy subjects. In particular, the frequencies of the -455G/A AA and -148C/T TT genotypes were significantly higher than in healthy subjects. Individuals carrying the A or T allele had a higher incidence of cerebral infarction compared with those carrying the G or C allele. Our experimental findings indicate that the -148C/T and -455G/A polymorphisms are associated with cerebral infarction in Xinjiang Uygur and Han Chinese subjects. The susceptibility- conferring alleles are -148T and -455A, and the susceptibility-conferring genotype is -455G/A + AA.
doi:10.3969/j.issn.1673-5374.2012.07.012
PMCID: PMC4349004  PMID: 25745443
Uygur; Han; cerebral infarction; β-fibrinogen gene; polymorphism; neural regeneration
21.  Dr.VIS: a database of human disease-related viral integration sites 
Nucleic Acids Research  2011;40(Database issue):D1041-D1046.
Viral integration plays an important role in the development of malignant diseases. Viruses differ in preferred integration site and flanking sequence. Viral integration sites (VIS) have been found next to oncogenes and common fragile sites. Understanding the typical DNA features near VIS is useful for the identification of potential oncogenes, prediction of malignant disease development and assessing the probability of malignant transformation in gene therapy. Therefore, we have built a database of human disease-related VIS (Dr.VIS, http://www.scbit.org/dbmi/drvis) to collect and maintain human disease-related VIS data, including characteristics of the malignant disease, chromosome region, genomic position and viral–host junction sequence. The current build of Dr.VIS covers about 600 natural VIS of 5 oncogenic viruses representing 11 diseases. Among them, about 200 VIS have viral–host junction sequence.
doi:10.1093/nar/gkr1142
PMCID: PMC3245036  PMID: 22135288
22.  Detection of Intra-Tumor Self Antigen Recognition during Melanoma Tumor Progression in Mice Using Advanced Multimode Confocal/Two Photon Microscope 
PLoS ONE  2011;6(6):e21214.
Determining how tumor immunity is regulated requires understanding the extent to which the anti-tumor immune response “functions” in vivo without therapeutic intervention. To better understand this question, we developed advanced multimodal reflectance confocal/two photon fluorescence intra-vital imaging techniques to use in combination with traditional ex vivo analysis of tumor specific T cells. By transferring small numbers of melanoma-specific CD8+ T cells (Pmel-1), in an attempt to mimic physiologic conditions, we found that B16 tumor growth alone was sufficient to induce naive Pmel-1 T cell proliferation and acquisition of effector phenotype. Tumor -primed Pmel-1 T cells, are capable of killing target cells in the periphery and secrete IFNγ, but are unable to mediate tumor regression. Within the tumor, Pmel-1 T cells have highly confined mobility, displaying long term interactions with tumor cells. In contrast, adoptively transferred non tumor-specific OT-I T cells show neither confined mobility, nor long term interaction with B16 tumor cells, suggesting that intra-tumor recognition of cognate self antigen by Pmel-1 T cells occurs during tumor growth. Together, these data indicate that lack of anti-tumor efficacy is not solely due to ignorance of self antigen in the tumor microenvironment but rather to active immunosuppressive influences preventing a protective immune response.
doi:10.1371/journal.pone.0021214
PMCID: PMC3120835  PMID: 21731676
23.  Agonist Anti-GITR Monoclonal Antibody Induces Melanoma Tumor Immunity in Mice by Altering Regulatory T Cell Stability and Intra-Tumor Accumulation 
PLoS ONE  2010;5(5):e10436.
In vivo GITR ligation has previously been shown to augment T-cell-mediated anti-tumor immunity, yet the underlying mechanisms of this activity, particularly its in vivo effects on CD4+ foxp3+ regulatory T cells (Tregs), have not been fully elucidated. In order to translate this immunotherapeutic approach to the clinic it is important gain better understanding of its mechanism(s) of action. Utilizing the agonist anti-GITR monoclonal antibody DTA-1, we found that in vivo GITR ligation modulates regulatory T cells (Tregs) directly during induction of melanoma tumor immunity. As a monotherapy, DTA-1 induced regression of small established B16 melanoma tumors. Although DTA-1 did not alter systemic Treg frequencies nor abrogate the intrinsic suppressive activity of Tregs within the tumor-draining lymph node, intra-tumor Treg accumulation was significantly impaired. This resulted in a greater Teff:Treg ratio and enhanced tumor-specific CD8+ T-cell activity. The decreased intra-tumor Treg accumulation was due both to impaired infiltration, coupled with DTA-1-induced loss of foxp3 expression in intra-tumor Tregs. Histological analysis of B16 tumors grown in Foxp3-GFP mice showed that the majority of GFP+ cells had lost Foxp3 expression. These “unstable” Tregs were absent in IgG-treated tumors and in DTA-1 treated TDLN, demonstrating a tumor-specific effect. Impairment of Treg infiltration was lost if Tregs were GITR−/−, and the protective effects of DTA-1 were reduced in reconstituted RAG1−/− mice if either the Treg or Teff subset were GITR-negative and absent if both were negative. Our results demonstrate that DTA-1 modulates both Teffs and Tregs during effective tumor treatment. The data suggest that DTA-1 prevents intra-tumor Treg accumulation by altering their stability, and as a result of the loss of foxp3 expression, may modify their intra-tumor suppressive capacity. These findings provide further support for the continued development of agonist anti-GITR mAbs as an immunotherapeutic strategy for cancer.
doi:10.1371/journal.pone.0010436
PMCID: PMC2862699  PMID: 20454651
25.  Correlation of clinical and immunological data in a metastatic melanoma patient with heterogeneous tumor responses to ipilimumab therapy 
Melanoma patients treated with anti-CTLA-4 have shown a range of anti-tumor responses. In this report, we describe the response of a single patient to anti-CTLA-4, with individual lesions disappearing, others stabilizing, and others progressing. These responses can be viewed as a clear manifestation of cancer immunoediting and its three phases of elimination, equilibrium and escape, with each tumor in this patient being at a discrete stage in the process. The patient's course and associated immunological monitoring and other laboratory data are presented in an immunogram, a way to visualize temporal associations between the multiple clinical and laboratory parameters.
PMCID: PMC2964016  PMID: 20052966
human; melanoma; ipilimumab; case report; immunogram; immunoediting

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