Search tips
Search criteria 


Logo of joncJournal of Oncology
J Oncol. 2010; 2010: 179491.
Published online 2010 June 29. doi:  10.1155/2010/179491
PMCID: PMC2910457

Advances in Cellular Therapy for the Treatment of Thyroid Cancer


Up to now, there are no curative therapies available for the subset of metastasized undifferentiated/anaplastic thyroid carcinomas. This review describes the possible use of immunocompetent cells which may help to restore the antitumor immune recognition for treating an existing tumor or preventing its recurrence. The most prominent experimental strategy is the use of dendritic cells (DCs) which are highly potent in presenting tumor antigens. Activated DCs subsequently migrate to draining lymph nodes where they present antigens to naïve lymphocytes and induce cytotoxic T cells (CTL). Alternatively to DC therapy, adoptive cell transfer may be performed by either using natural killer cells or ex vivo maturated CTLs. Within this review article we will focus on recent advances in the understanding of anti-tumor immune responses, for example, in thyroid carcinomas including the advances which have been made for the identification of potential tumor antigens in thyroid malignancies.

1. Introduction

The most frequently occurring forms of thyroid cancer have a good prognosis. The neoplasms originate from two distinct endocrine cell types of the thyroid gland: thyroid hormone producing follicular epithelial cells and calcitonin-producing parafollicular cells (C-cells). The most prevalent thyroid cancer is that of papillary origin (PTC; about 60–80%) it differs from follicular (FTC; 15–25%) and anaplastic carcinomas (ATC; 2–5%) but all are derived also from follicular epithelial cells. Only about 3–10% of the thyroid tumors derive from parafollicular C-cells. These tumors are termed as medullary thyroid carcinoma (MTC) [1, 2].

The good prognosis of PTC and FTC is originally attributed to the steady growth rate and the competence of taking up iodide. This leads to the potential classical therapeutic option of radioiodide (131I-) treatment after a surgical revision of the tumor mass [3]. The varieties of the different tumors of follicular origin reveal in their distinct morphology, their kind of metastatic spreading, and their molecular alterations leading to different pathways involved in the boost of cell proliferation [4].

The carcinoma bearing the worst prognosis is ATC which nearly almost derive de novo or rarely from pre-existing PTC or FTC from which it may dedifferentiate sometimes revealing transitional stages [5, 6] and, however, may develop into highly malignant ATC with low survival rates. ATC have a high mitotic rate with both hematological and lymphovascular invasions and do not retain any of the biological features of the original follicular cells, such as uptake of iodine and synthesis of thyroglobulin [7]. Due to their molecular alterations and biological inoperable feature these tumors are inaccessible to classical treatment options such as radio- and chemotherapy [8]. New drugs, such as fosbretabulin [9], bortezomib, and TNF-related apoptosis induced ligand (TRAIL) [10] are now introduced and trialed in clinical labs and human clinical studies.

Beside, MTC might also have a good prognosis when it is restricted to the thyroid gland itself [11]. In case of distant metastases moieties of the patients develop a rapidly progressing disease leading to death. Clinical management of this disease is possible only by monitoring the location and expansion of the tumor mass and metastases followed by an extensive surgery and by observing antigens like calcitonin or carcinoembryonic antigen during the follow up [12].

Especially for the noncurative thyroid tumors such as ATC and all invasive and metastasized PTC and FTC it is of substantial interest to develop new approaches for the treatment of these cancers. Here, we can learn from immunological interventions which have already been applied to patients with other nonendocrine and endocrine cancers including MTC.

2. Advances in Cellular Therapy

An alternative approach for the treatment of cancers may represent the use of cell vaccines aiming to activate the immune system. Antitumor immunity is coordinated by both innate and adaptive immunity, and mainly mediated by cytotoxic T cells (CTLs), natural killer (NK), and natural killer T (NKT) cells. The induction and coordination within this context is arranged by dendritic cells (DCs) [13, 14]. DCs are highly potent antigen-presenting cells with the ability of taking up and processing tumor antigens in the peripheral blood and tissues. They subsequently migrate to the draining lymph nodes to present antigens to naïve T lymphocytes and induce a cellular immune response by direct priming of CD8+ CTLs and a cross-presentation involving CD4+ helper cells. Moreover, DCs are also important in inducing humoral immunity as explained by their capacity to activate naïve and memory B cells [15] and NK [16] as well as NKT cells [17]. Thus, DCs can modulate the whole immune repertoire they represent an excellent tool for treating an existing tumor or preventing its recurrence.

In vivo, two main pathways of DC differentiation have been described depending on their cell lineage and the tissue were they are activated [18]. Under in vitro conditions, myeloid DCs may be generated from monocytes by activating with granulocyte/macrophage colony-stimulating factor (GM-CSF). The monocytes which encounter interleukin-4 (IL-4) become DCs known as IL-4-DCs [1921]. On the other hand, monocytes differentiate into different DC subsets after costimulation with other cytokines such as IFN-α, TNF or IL-15 [2228]. One essential precondition for the success is the priming of DC with special tumor associated antigens (TAA). These TAA must bear high immunogenic properties against the background of HLA restriction. In this context, the broadest experience has been gained for the therapy of malignant melanoma [2933] as well as in renal cell carcinoma [3438]. Even though only limited success has been achieved from the clinical point of view, DC vaccinations are superior compared to other antitumor vaccination strategies [39]. Importantly, DC vaccination strategies have steadily been improved by the number of immunocompetent tumor antigens identified thus far [4043], even in endocrine malignacies [44]. One way of assessing tumor antigens is based on the use of computer-based algorithm software namely SYFPEITHI or BIMAS [4548] which helps to predict immunocompetent tumor epitopes. Examples of classical tumor epitopes are those of MAGE, GAGE, and NY-ISO1 in malignant melanoma [4955].

Alternatively to DC therapy, new strategies were introduced using antigen-specific CTLs or potent NK cells to burst the immune tolerance. Adoptive T-cell immunotherapy is mainly performed by the generation of large numbers of antigen-specific CTLs. But both tumor-specific CD4+ helper 1 (Th1) cells and cytotoxic CD8+ T cells might be generated in vitro and administered directly to patients [56, 57]. Maturation of specific lymphocytes were performed by ex vivo exposure to cytokines, HLA-restricted antigen epitopes, and either in vitro generated DCs [57, 58] or with CD3 and/or CD28-specific mAb [58, 59].

On the other hand, NK cells are the major representatives of the innate immune system that is regulated by positive and negative mechanisms. NK cells interact with tumor cells through activating receptors of the immunoglobulin superfamily (NKp30, NKp44, NKp46, NKG2D) and the lectin-like type II transmembrane proteins exhibiting a C-type lectin domain (CD94, CD161), and on the other hand, through inhibitory receptors (KIR, e.g., NKG2A) which primarily bind to MHC class I antigens on target cells [60, 61]. Moreover, NK cells express CD16 which serves as a receptor for antibodies to home on target cells performing the antibody dependent cellular cytotoxicity [62, 63].

Within the last decade a multitude of different studies and clinical trails have been performed using cell therapies [6467]. Cancer immunotherapy using DC or adoptive CTLs has much promise because malignant cells can be affected by the immune system without damaging healthy tissue and without dangerous side effects. Nevertheless, careful monitoring of the elicited T-cell response and quality assurance is mandatory to establish a rationale for specific immunotherapy and to bring it from bench to bedside [68, 69]. In any case, the identification of tumor cell specific antigens is crucial for establishing clinically effective tumor immunotherapies and monitoring the induced immune response, including quantification of antigen-specific CTLs. Other approaches might use NK or NK-T cells, respectively, however with less experiments compared to DC vaccinations [70, 71].

3. Experience in Cellular Therapies for Medullary Thyroid Carcinoma

The idea of using polypeptide hormones as tumor antigens for cancer therapy resulted from the observation in autoimmunity, where responses to self tissue antigens led to tissue damage. The most intensively investigated autoimmune disease is T1DM, which is characterized by infiltration of pancreatic islets by self-reactive lymphocytes, leading to destruction of insulin-secreting β-cells. Insulin itself is probably the most important autoantigen described thus far [72]. This is supported by the fact that many reactive T cells invading pancreatic islets are specific for immune insulin epitopes and are capable of adoptively transferring diabetes in non-obese diabetic (NOD) mice [73, 74].

This violability of the immune system leads to the option to reconstitute immunity by antitumor immunotherapy. One goal was scored by the work of Bradwell and Harvey identifying the use of polypeptide hormones as tumor antigens [75]. They were first to apply a combination of synthetic human and bovine parathyroid hormone (PTH) peptides for vaccination of one patient with metastatic parathyroid cancer. They demonstrated increased PTH-specific antibody titers, resulting in a notable decrease in serum calcium levels and a relief of clinical symptoms. Nonetheless, no association with reduced tumor mass was observed. Thereafter, Betea et al. [76] performed an immunization trial with bovine and human PTH fragments and with intact full-length human PTH. The effect of this treatment was a specific antibody production to all PTH fragments, resulting in largely diminished PTH and serum calcium levels. Most importantly, they observed a remarkable decrease in tumors of pulmonary metastases, indicating a PTH specific cytotoxic immune response.

Based on this knowledge, the polypeptide hormone calcitonin has been proposed as tumor antigen for immunotherapy in MTC. Since then, several vaccination trials have been performed in murine models and as well in man. Vaccination studies with CT-loaded DCs were performed in a transgenic mouse model for MTC mice displaying the identical mutation (substitution of Cys for Arg) within the RET protooncogene at codon 634 as most patients with multiple endocrine neoplasia type 2A [77, 78]. As in patients with hereditary MTC, Ret/Cal mice develop diffuse C cell hyperplasia and MTC with increased serum CT levels [77]. Depending on the CT epitopes used epitope specific CD8+ CTLs were visualized via tetramer analyses and by functional lysis assays. These results were accompanied by a largely diminished tumor outgrowth [79, 80].

In humans, several studies used full-length CT for priming DCs [81, 82]. Importantly, in one patient, a remarkable transient regression of pulmonary and liver metastases was seen. Detailed in vitro analyses revealed a CT-specific T-cell reactivity, which was Th1-driven, in some patients, as determined by a large increase in IFN-γ production [83]. Thereafter, a new protocol with interferon-α generated DCs with direct tumor lysis activity was performed [84]. These cells were also loaded with full-length CT [85]. After a long-term follow-up of more than 48 months, two of five MTC patients showed stable disease with changes in tumor size and tumor marker of less than 25%. This is important because it shows a direct connection between induction of cytotoxic immunity and clinical response [85].

4. Potential Tumor Antigens in Poorly Differentiated Thyroid Carcinomas

Tumor-associated antigens (TAA) are surface-associated molecules such as receptors, transmembrane proteins or secreted/membrane-attached peptides that are mostly cancer specific, often overexpressed and recognized by the immune system [120]. Therefore, identifying specific TAA is of key importance for developing new options for immunotherapy for incurable cancers. Up to now, however, no single TAA for primary thyroid carcinomas have been proven but there are a couple of candidates which might have the potential to become one.

Potential tumor antigens which might represent a distinct tumor association can be divided into the groups of classical cancer testes antigens, specific receptors, functional-associated proteins, and metastases-associated proteins. Find an assembly of potential TAA and of already performed experiments in Table 1.

Table 1
List of possible thyroid tumor associated antigens.

The most prominent tumor antigens are certainly the cancer testes antigens, which have already been identified in many malignancies and which have intensively used in the context of immunotherapy [3133, 4042, 5052]. These antigens belong to a gene family which has been reported to be expressed in tumor cells but not in normal tissues aside from the testicular germ cells where the absence of MHC class-I molecules protect the cells from testicular autoimmunity, as the antigenic peptides are not be displayed at the cell surface [121]. This makes these TAA so attractive for immunotherapy since no side effects are expected. In PTC and FTC the cancer testis genes MAGE and GAGE were identified in human thyroid carcinomas [8688]. For instance, MAGE-3 is detectable in 29% of follicular tumor tissue and in 80% in papillary thyroid carcinomas. This observation explores the possibility of specific immunotherapy using these TAA for vaccination trails.

Another group of potential tumor antigens represent the large group of receptors. The main player are the IGF-I receptor in thyroid carcinomas [89, 90, 122] and the receptor tyrosine kinases as EGF-R, PDGF-R α & β, VEGF-R 1&2, c-KIT especially in FTC and some ATC [91, 93, 94]. Whether these receptors are likely to be used as tumor antigens has still to be proven. IGF-I is known to have significant effects on cell proliferation and differentiation, it is a potent mitogen, a powerful inhibitor of programmed cell death, and has a well-established role in the transformation of normal to malignant cells. So, especially the overexpression of the IGF-I receptor might have a possible target function while its presence is important for the development of a malignant phenotype [89, 123]. Up to now, however, only antibody-based therapies were performed [90, 124].

Other receptors untypically expressed in thyroid carcinomas might also be considered. For example, CD10 a common antigen for acute lymphoblastic leukemia has been found to be useful in the differential diagnosis of malignancy. Moreover, it has been shown to be expressed in a group of PTC as well as in papillary microcarcinomas [95] and in some FTC [96]. Several reports implicated the chemokine receptor CXCR4 in thyroid tumor aggressiveness. The target for CXCR4 is the chemokine CXCL12/SDF-1 α & β involved in both embryonic and tumor angiogenesis [97]. This receptor might be also a potent target for a direct CTL offense.

In 2007, characteristic biomarkers were described for PTC lymph node metastasis [98]. By real-time reverse transcription-PCR and immunohistochemistry three genes were discovered consistently overexpressed in lymph node metastasis. Especially, LIM (kinase) domain containing 2 (LIMD2) and the protein tyrosine phosphatase receptor type C (PTPRC also known as CD45) were significantly different expressed in tumor samples versus metastatic samples. Additionally, lymphotoxin beta (LTB), a type II membrane anchored protein of the TNF family had borderline significance. Since there are no antibodies for LIMD2, only PTPRC and LTB could be tested by immunohistochemistry. All samples tested, showed both proteins in metastases and little or no expression in primary tumor.

Moreover, there are the so-called functional-associated antigens. PTC and FTC derive from thyroid epithelial cells resulting in a large expression of thyreoglobulin which also represent a classical tumor marker [99, 100, 125, 126]. Whether thyroglobulin also represents a tumor antigen needs, however, to be proven.

Beside, a couple of other antigens have recently been described for thyroid carcinomas. One of those is a biomarker for the malignancy status of PTC and FTC. The human mesothelial cell marker 1 (HBME-1) have originally been decribed in mesotheliomas. Meanwhile, it is known that it is expressed in 90 to 100% of the carcinomas with a strong membrane staining [102, 103]. Additionally, several other antigens are on debate like human type I cytokeratin 19 (CK19), galectin-7, and probably galectin-3 which are overexpressed in papillary and follicular malignancies [102, 127, 128]. CK19 is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells and is highly expressed by differentiated thyroid carcinomas, mainly of the papillary subtype. The soluble fragments of CK19 can already be measured by immunometric assays [129]. Galectins are a structurally related family of lectin proteins that bind specifically to beta-galactoside in a calcium-independent manner; originally they are cytosolic proteins involved in growth regulation and internal processes such as pre-mRNA splicing [130] but they are able to translocate into vesicles due to participate in cell-cell and cell-matrix adhesion [130, 131]. Moreover, elevated levels of fibronectin-1 might be a good target due to its alternative splicing during tumorigenic process which leads to different isoforms of extracellular domains or connecting segments [101, 102]. Likewise, two other TAA which have a broad expression pattern in many types of human malignancies are now described in thyroid carcinomas as well. One is survivin which is overexpressed in poorly differentiated thyroid cancers inducing antiapoptotic processes [104] and the telomerase reverse transcriptase (TERT), that is, concomitant in cancer cells responsible for the stabilization of the telomeres receiving an immortalization of the respective cells [105108]. Both antigens where already used as targets for several vaccination studies in melanomas and breast cancer [132137].

Finally, there is the group of metastases-associated proteins. The growth of a neoplasm and its ability to metastasize is a multistep process dependent on angiogenesis and immunological reactions of the organism. In this process, adhesive factors like soluble intercellular adhesion molecules (sICAM-1) and vascular cellular adhesion molecules (sVCAM-1) are involved. The serum of peripheral blood of patients with thyroid cancer before surgery revealed these factors in a significant higher concentration compared to controls [138]. Since these soluble factors are egested by the tumor itself and might also be associated to the membrane exhibiting a potent tumor antigen.

Aside, several other factors are described being involved in invasion and metastasis. One main component is the group of matrix metalloproteinases (MMPs) since they disrupt extracellular matrix proteins. An increase of circulating MMP-2 [109, 110, 139, 140], MMP-7 [110, 111], and MMP-9 [110, 112, 141] was affirmed manifold. In this context, CD147 one of the molecules involved in regulating the expression MMP-2 was described to be expressed more frequently in PTC and ATC patients and is associated with their clinicopathologic features [109]. Additionally, the urokinase-type plasminogen activator (u-PA) and its specific receptor (u-PA-R) are involved in the disruption of the extracellular matrix which relies on the activation of plasminogen and an interaction with MMPs [112, 113]. One report advised on an antigen, namely, fascin which is markedly upregulated in more than 60% PTC. It is displaying an actin-bundling protein, however, associated with high-grade extensive invasion [114].

5. Special Situation in Anaplastic Thyroid Carcinoma

In ATC, a multitude of molecular alterations are found [142, 143] but only a small number of potential antigens have been described. Nonetheless, some potential antigens discovered for FTC and PTC are also found in ATC although molecular variances may also lead to a downregulation of those. The most prominent loss is described for c-Kit which was monitored to be absent in most ATC [144, 145].

Two additional proteins were recently found in ATC. One is called autotaxin which has a nucleotide pyrophosphatase/phosphodiesterase and lysophospholipase D activity. It is usually secreted but also membrane-associated and is a highly bioactive enhancer for motility of thyroid tumors [115, 116]. Beside, expression of CD133 displaying a hematopoietic stem cells antigen was described in tumor derived cells lines [117, 118].

6. Future Perspectives

The research for cellular cancer therapy has bred some promising approaches but until now no single vaccination regimen tested is indicated as a standard anticancer therapy. In order to circumvent the escape of thyroid tumor cells under T-cell pressure, polyvalent vaccination strategies may help to overcome this situation. This goal can be achieved by either loading DCs with a pool of peptide antigens which might be individually identified as TAAs or by adoptive CTL or NK/NK-T cell transfer. The major drawback in many human malignancies including thyroid tumors is, however, the lack of established tumor antigens which, in addition, have already been applied in clinical context. As mentioned above, a multitude of proteins and receptors have been described to be overexpressed in a certain percentage of these thyroid tumors. Whether some of those are true TAAs recognized from cells of the adaptive immune system is still elusive and needs to be clarified. Not till then, they could be used in clinical trials in humans. Nonetheless, it is necessary to search for other potential tumor antigens. Within this context, novel technologies, that is, high-throughput gene microarray, should further be implemented in order to identify new antigens.

Another way of improving present treatment concepts is to use a combination therapy by which tumor cells are selectively affected and the tumor escape mechanisms are accessory blocked or decreased [146]. In this context, conventional chemotherapy has already been supported by a combination with DC vaccination showing some clinical benefits in nonendocrine tumors [147149]. In endocrine (e.g., thyroid) tumors such data does, however, not exist. More relevant, however, might be a combination of cellular immunotherapy and tyrosine kinase inhibitors (TKIs) affecting target-specific agents. In thyroid malignancies different TKIs particularly sorafenib, motesanib, vatalanib, and so forth, have already been applied in clinical studies [150152]. Although TKIs have been described to deplete immunoregulatory, for example, regulatory T cells they also have an effect on all T cells and DCs [153, 154] but interestingly not on NK cells [155]. On the other hand, TKIs' affect DCs to activate NK cells [156158]. The depletion of T cells by TKIs also resulted in a reconstitution with a predominant expansion of antigen-specific T cells [159] and the higher binding capacity of CTLs to MHC presenting antigens [160]. So, the combination of cellular therapies with targeted molecules including TKIs hold promise for successful cancer therapies in the future.


M.S. has been supported by the Wilhelm Sander Foundation (No. L008.002.1).


1. Benvenga S. Update on thyroid cancer. Hormone and Metabolic Research. 2008;40(5):323–328. [PubMed]
2. Zhu XG, Cheng SY. Modeling thyroid cancer in the mouse. Hormone and Metabolic Research. 2009;41(6):488–499. [PMC free article] [PubMed]
3. Sipos JA, Mazzaferri EL. The therapeutic management of differentiated thyroid cancer. Expert Opinion on Pharmacotherapy. 2008;9(15):2627–2637. [PubMed]
4. Vasko VV, Saji M. Molecular mechanisms involved in differentiated thyroid cancer invasion and metastasis. Current Opinion in Oncology. 2007;19(1):11–17. [PubMed]
5. Chiacchio S, Lorenzoni A, Boni G, Rubello D, Elisei R, Mariani G. Anaplastic thyroid cancer: prevalence, diagnosis and treatment. Minerva Endocrinologica. 2008;33(4):341–357. [PubMed]
6. Ziad EA, Ruchala M, Breborowicz J, Gembicki M, Sowinski J, Grzymislawski M. Immunoexpression of TTF-1 and Ki-67 in a coexistent anaplastic and follicular thyroid cancer with rare long-life surviving. Folia Histochemica et Cytobiologica. 2008;46(4):461–464. [PubMed]
7. Haigh PI. Anaplastic thyroid carcinoma. Current Treatment Options in Oncology. 2000;1(4):353–357. [PubMed]
8. Smallridge RC, Marlow LA, Copland JA. Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies. Endocrine-Related Cancer. 2009;16(1):17–44. [PMC free article] [PubMed]
9. Mooney CJ, Nagaiah G, Fu P, et al. A phase II trial of fosbretabulin in advanced anaplastic thyroid carcinoma and correlation of baseline serum-soluble intracellular adhesion molecule-1 with outcome. Thyroid. 2009;19(3):233–240. [PMC free article] [PubMed]
10. Conticello C, Adamo L, Giuffrida R, et al. Proteasome inhibitors synergize with tumor necrosis factor-related apoptosis-induced ligand to induce anaplastic thyroid carcinoma cell death. Journal of Clinical Endocrinology and Metabolism. 2007;92(5):1938–1942. [PubMed]
11. van Veelen W, De Groot JWB, Acton DS, et al. Medullary thyroid carcinoma and biomarkers: past, present and future. Journal of Internal Medicine. 2009;266(1):126–140. [PubMed]
12. Favia G, Iacobone M, Zanella S, Ciarleglio FA. Management of invasive and advanced thyroid cancer. Minerva Endocrinologica. 2009;34(1):37–55. [PubMed]
13. Banchereau J, Ueno H, Dhodapkar M, et al. Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon. Journal of Immunotherapy. 2005;28(5):505–516. [PubMed]
14. Steinman RM. The dendritic cell system and its role in immunogenicity. Annual Review of Immunology. 1991;9:271–296. [PubMed]
15. Jego G, Palucka AK, Blanck J-P, Chalouni C, Pascual V, Banchereau J. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity. 2003;19(2):225–234. [PubMed]
16. Fernandez NC, Lozier A, Flament C, et al. Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nature Medicine. 1999;5(4):405–411. [PubMed]
17. Kadowaki N, Antonenko S, Liu Y-J. Distinct CpG DNA and polyinosinic-polycytidylic acid double-stranded RNA, respectively, stimulate CD11c- type 2 dendritic cell precursors and CD11c+ dendritic cells to produce type I IFN. Journal of Immunology. 2001;166(4):2291–2295. [PubMed]
18. Schott M. Immunesurveillance by dendritic cells: potential implication for immunotherapy of endocrine cancers. Endocrine-Related Cancer. 2006;13(3):779–795. [PubMed]
19. Peters JH, Xu H, Ruppert J, Ostermeier D, Friedrichs D, Gieseler RKH. Signals required for differentiating dendritic cells from human monocytes in vitro. Advances in Experimental Medicine and Biology. 1993;329:275–280. [PubMed]
20. Romani N, Gruner S, Brang D, et al. Proliferating dendritic cell progenitors in human blood. Journal of Experimental Medicine. 1994;180(1):83–93. [PMC free article] [PubMed]
21. Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α . Journal of Experimental Medicine. 1994;179(4):1109–1118. [PMC free article] [PubMed]
22. Jacobs B, Wuttke M, Papewalis C, Seissler J, Schott M. Dendritic cell subtypes and in vitro generation of dendritic cells. Hormone and Metabolic Research. 2008;40(2):99–107. [PubMed]
23. Luft T, Pang KC, Thomas E, et al. Type I IFNs enhance the terminal differentiation of dendritic cells. Journal of Immunology. 1998;161(4):1947–1953. [PubMed]
24. Paquette RL, Hsu NC, Kiertscher SM, et al. Interferon-α and granulocyte-macrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigen-presenting cells. Journal of Leukocyte Biology. 1998;64(3):358–367. [PubMed]
25. Santini SM, Lapenta C, Logozzi M, et al. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. Journal of Experimental Medicine. 2000;191(10):1777–1788. [PMC free article] [PubMed]
26. Jacobs B, Wuttke M, Papewalis C, et al. Characterization of monocyte-derived IFNα-generated dendritic cells. Hormone and Metabolic Research. 2008;40(2):117–121. [PubMed]
27. Chomarat P, Dantin C, Bennett L, Banchereau J, Palucka AK. TNF skews monocyte differentiation from macrophages to dendritic cells. Journal of Immunology. 2003;171(5):2262–2269. [PubMed]
28. Mohamadzadeh M, Berard F, Essert G, et al. Interleukin 15 skews monocyte differentiation into dendritic cells with features of langerhans cells. Journal of Experimental Medicine. 2001;194(7):1013–1020. [PMC free article] [PubMed]
29. Di Pucchio T, Pilla L, Capone I, et al. Immunization of stage IV melanoma patients with Melan-A/MART-1 and gplOO peptides plus IFN-α results in the activation of specific CD8+ T cells and monocyte/dendritic cell precursors. Cancer Research. 2006;66(9):4943–4951. [PubMed]
30. Jacobs JFM, Aarntzen EHJG, Sibelt LAG, et al. Vaccine-specific local T cell reactivity in immunotherapy-associated vitiligo in melanoma patients. Cancer Immunology, Immunotherapy. 2009;58(1):145–151. [PubMed]
31. Jäger E, Karbach J, Gnjatic S, et al. Recombinant vaccinia/fowlpox NY-ESO-1 vaccines induce both humoral and cellular NY-ESO-1-specific immune responses in cancer patients. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(39):14453–14458. [PubMed]
32. Odunsi K, Qian F, Matsuzaki J, et al. Vaccination with an NY-ESO-1 peptide of HLA class I/II specificities induces integrated humoral and T cell responses in ovarian cancer. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(31):12837–12842. [PubMed]
33. Valmori D, Souleimanian NE, Tosello V, et al. Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-priming. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(21):8947–8952. [PubMed]
34. Asemissen AM, Brossart P. Vaccination strategies in patients with renal cell carcinoma. Cancer Immunology, Immunotherapy. 2009;58(7):1169–1174. [PubMed]
35. Brossart P. Dendritic cells in vaccination therapies of malignant diseases. Transfusion and Apheresis Science. 2002;27(2):183–186. [PubMed]
36. Höltl L, Ramoner R, Zelle-Rieser C, et al. Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide. Cancer Immunology, Immunotherapy. 2005;54(7):663–670. [PubMed]
37. Schendel DJ. Dendritic cell vaccine strategies for renal cell carcinoma. Expert Opinion on Biological Therapy. 2007;7(2):221–232. [PubMed]
38. Wierecky J, Müller MR, Wirths S, et al. Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. Cancer Research. 2006;66(11):5910–5918. [PubMed]
39. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nature Medicine. 2004;10(9):909–915. [PMC free article] [PubMed]
40. Akiyama Y, Tanosaki R, Inoue N, et al. Clinical response in Japanese metastatic melanoma patients treated with peptide cocktail-pulsed dendritic cells. Journal of Translational Medicine. 2005;3(1):p. 4. [PMC free article] [PubMed]
41. Akiyama Y, Maruyama K, Tai S, et al. Characterization of a MAGE-1-derived HLA-A24 epitope-specific CTL Line from a Japanese metastatic melanoma patient. Anticancer Research. 2009;29(2):647–655. [PubMed]
42. Fuessel S, Meye A, Schmitz M, et al. Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: results of a phase I clinical trial. Prostate. 2006;66(8):811–821. [PubMed]
43. Waeckerle-Men Y, Uetz-Von Allmen E, Fopp M, et al. Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma. Cancer Immunology, Immunotherapy. 2006;55(12):1524–1533. [PubMed]
44. Sbiera S, Wortmann S, Fassnacht M. Dendritic cell based immunotherapy—a promising therapeutic approach for endocrine malignancies. Hormone and Metabolic Research. 2008;40(2):89–98. [PubMed]
45. Asemissen AM, Haase D, Stevanovic S, et al. Identification of an immunogenic HLA-A*0201-binding t-cell epitope of the transcription factor PAX2. Journal of Immunotherapy. 2009;32(4):370–375. [PubMed]
46. Dick TP, Stevanović S, Keilholz W, et al. The making of the dominant MHC class I ligand SYFPEITHI. European Journal of Immunology. 1998;28(8):2478–2486. [PubMed]
47. Mishra S, Sinha S. Prediction and molecular modeling of T-cell epitopes derived from placental alkaline phosphatase for use in cancer immunotherapy. Journal of Biomolecular Structure and Dynamics. 2006;24(2):109–121. [PubMed]
48. Parker KC, Bednarek MA, Coligan JE. Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. Journal of Immunology. 1994;152(1):163–175. [PubMed]
49. Adams S, O’Neill DW, Nonaka D, et al. Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. Journal of Immunology. 2008;181(1):776–784. [PMC free article] [PubMed]
50. Barrow C, Browning J, MacGregor D, et al. Tumor antigen expression in melanoma varies according to antigen and stage. Clinical Cancer Research. 2006;12(3 part 1):764–771. [PubMed]
51. Bazhin AV, Wiedemann N, Schnölzer M, Schadendorf D, Eichmüller SB. Expression of GAGE family proteins in malignant melanoma. Cancer Letters. 2007;251(2):258–267. [PubMed]
52. Connerotte T, Van PA, Godelaine D, et al. Functions of anti-MAGE T-cells induced in melanoma patients under different vaccination modalities. Cancer Research. 2008;68(10):3931–3940. [PubMed]
53. Coulie PG, Karanikas V, Lurquin C, et al. Cytolytic T-cell responses of cancer patients vaccinated with a MAGE antigen. Immunological Reviews. 2002;188:33–42. [PubMed]
54. Joyner DE, Damron TA, Aboulafia A, Bokor W, Bastar JD, Randall RL. Heterogeneous expression of melanoma antigen (hMAGE) mRNA in mesenchymal neoplasia. Tissue Antigens. 2006;68(1):19–27. [PubMed]
55. Vence L, Palucka AK, Fay JW, et al. Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma. Proceedings of the National Academy of Sciences of the United States of America. 2007;104(52):20884–20889. [PubMed]
56. Hunder NN, Wallen H, Cao J, et al. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. New England Journal of Medicine. 2008;358(25):2698–2703. [PMC free article] [PubMed]
57. Mackensen A, Meidenbauer N, Vogl S, Laumer M, Berger J, Andreesen R. Phase I study of adoptive T-cell therapy using antigen-specific CD8+ T cells for the treatment of patients with metastatic melanoma. Journal of Clinical Oncology. 2006;24(31):5060–5069. [PubMed]
58. Oelke M, Maus MV, Didiano D, June CH, Mackensen A, Schneck JP. Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig-coated artificial antigen-presenting cells. Nature Medicine. 2003;9(5):619–624. [PubMed]
59. Kurokawa T, Oelke M, Mackensen A. Induction and clonal expansion of tumor-specific cytotoxic T lymphocytes from renal cell carcinoma patients after stimulation with autologous dendritic cells loaded with tumor cells. International Journal of Cancer. 2001;91(6):749–756. [PubMed]
60. Joncker NT, Raulet DH. Regulation of NK cell responsiveness to achieve self-tolerance and maximal responses to diseased target cells. Immunological Reviews. 2008;224(1):85–97. [PMC free article] [PubMed]
61. Lanier LL. Up on the tightrope: natural killer cell activation and inhibition. Nature Immunology. 2008;9(5):495–502. [PMC free article] [PubMed]
62. Iannello A, Ahmad A. Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies. Cancer and Metastasis Reviews. 2005;24(4):487–499. [PubMed]
63. Klingemann H, Boissel L. Targeted cellular therapy with natural killer cells. Hormone and Metabolic Research. 2008;40(2):122–125. [PubMed]
64. Sorg RV, Özcan Z, Brefort T, et al. Clinical-scale generation of dendritic cells in a closed system. Journal of Immunotherapy. 2003;26(4):374–383. [PubMed]
65. Berger TG, Strasser E, Smith R, et al. Efficient elutriation of monocytes within a closed system (Elutra) for clinical-scale generation of dendritic cells. Journal of Immunological Methods. 2005;298(1-2):61–72. [PubMed]
66. Erdmann M, Dörrie J, Schaft N, et al. Effective clinical-scale production of dendritic cell vaccines by monocyte elutriation directly in medium, subsequent culture in bags and final antigen loading using peptides or RNA transfection. Journal of Immunotherapy. 2007;30(6):663–674. [PubMed]
67. Schadendorf D, Ugurel S, Schuler-Thurner B, et al. Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG. Annals of Oncology. 2006;17(4):563–570. [PubMed]
68. Meehan KR, Wu J, Webber SM, Barber A, Szczepiorkowski ZM, Sentman C. Development of a clinical model for ex vivo expansion of multiple populations of effector cells for adoptive cellular therapy. Cytotherapy. 2008;10(1):30–37. [PubMed]
69. Mueller MM, Seifried E. Blood transfusion in Europe: basic principles for initial and continuous training in transfusion medicine: an approach to an European harmonisation. Transfusion Clinique et Biologique. 2006;13(5):282–289. [PubMed]
70. Ayello J, van de Ven C, Cairo E, et al. Characterization of natural killer and natural killer-like T cells derived from ex vivo expanded and activated cord blood mononuclear cells: implications for adoptive cellular immunotherapy. Experimental Hematology. 2009;37(10):1216–1229. [PubMed]
71. Subleski JJ, Wiltrout RH, Weiss JM. Application of tissue-specific NK and NKT cell activity for tumor immunotherapy. Journal of Autoimmunity. 2009;33(3-4):275–281. [PMC free article] [PubMed]
72. Zhang L, Nakayama M, Eisenbarth GS. Insulin as an autoantigen in NOD/human diabetes. Current Opinion in Immunology. 2008;20(1):111–118. [PMC free article] [PubMed]
73. de Marquesini LGP, Moustakas AK, Thomas IJ, Wen L, Papadopoulos GK, Wong FS. Functional inhibition related to structure of a highly potent insulin-specific CD8 T cell clone using altered peptide ligands. European Journal of Immunology. 2008;38(1):240–249. [PMC free article] [PubMed]
74. Wong FS, Karttunen J, Dumont C, et al. Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library. Nature Medicine. 1999;5(9):1026–1031. [PubMed]
75. Bradwell AR, Harvey TC. Control of hypercalcaemia of parathyroid carcinoma by immunisation. Lancet. 1999;353(9150):370–373. [PubMed]
76. Betea D, Bradwell AR, Harvey TC, et al. Hormonal and biochemical normalization and tumor shrinkage induced by anti-parathyroid hormone immunotherapy in a patient with metastatic parathyroid carcinoma. Journal of Clinical Endocrinology and Metabolism. 2004;89(7):3413–3420. [PubMed]
77. Michiels F-M, Chappuis S, Caillou B, et al. Development of medullary thyroid carcinoma in transgenic mice expressing the RET protooncogene altered by a multiple endocrine neoplasia type 2A mutation. Proceedings of the National Academy of Sciences of the United States of America. 1997;94(7):3330–3335. [PubMed]
78. Machens A, Niccoli-Sire P, Hoegel J, et al. Early malignant progression of hereditary medullary thyroid cancer. New England Journal of Medicine. 2003;349(16):1517–1525. [PubMed]
79. Papewalis C, Wuttke M, Seissler J, et al. Dendritic cell vaccination with xenogenic polypeptide hormone induces tumor rejection in neuroendocrine cancer. Clinical Cancer Research. 2008;14(13):4298–4305. [PubMed]
80. Wuttke M, Papewalis C, Meyer Y, et al. Amino acid-modified calcitonin immunization induces tumor epitope-specific immunity in a transgenic mouse model for medullary thyroid carcinoma. Endocrinology. 2008;149(11):5627–5634. [PubMed]
81. Schott M, Feldkamp J, Klucken M, Kobbe G, Scherbaum WA, Seissler J. Calcitonin-specific antitumor immunity in medullary thyroid carcinoma following dendritic cell vaccination. Cancer Immunology, Immunotherapy. 2002;51(11-12):663–668. [PubMed]
82. Schott M, Seissler J, Lettmann M, Fouxon V, Scherbaum WA, Feldkamp J. Immunotherapy for medullary thyroid carcinoma by dendritic cell vaccination. Journal of Clinical Endocrinology and Metabolism. 2001;86(10):4965–4969. [PubMed]
83. Schattenberg D, Schott M, Reindl G, et al. Response of human monocyte-derived dendritic cells to immunostimulatory DNA. European Journal of Immunology. 2000;30(10):2824–2831. [PubMed]
84. Papewalis C, Jacobs B, Wuttke M, et al. IFN-α skews monocytes into CD56+-expressing dendritic cells with potent functional activities in vitro and in vivo. Journal of Immunology. 2008;180(3):1462–1470. [PubMed]
85. Papewalis C, Wuttke M, Jacobs B, et al. Dendritic cell vaccination induces tumor epitope-specific Th1 immune response in medullary thyroid carcinoma. Hormone and Metabolic Research. 2008;40(2):108–116. [PubMed]
86. Cheng S, Liu W, Mercado M, Ezzat S, Asa SL. Expression of the melanoma-associated antigen is associated with progression of human thyroid cancer. Endocrine-Related Cancer. 2009;16(2):455–466. [PubMed]
87. Ruschenburg I, Kubitz A, Schlott T, Korabiowska M, Droese M. MAGE-1, GAGE-1/-2 gene expression in FNAB of classic variant of papillary thyroid carcinoma and papillary hyperplasia in nodular goiter. International Journal of Molecular Medicine. 1999;4(4):445–448. [PubMed]
88. Milkovic M, Sarcevic B, Glavan E. Expression of MAGE tumor-associated antigen in thyroid carcinomas. Endocrine Pathology. 2006;17(1):45–52. [PubMed]
89. Chakravarty G, Santillan AA, Galer C, et al. Phosphorylated insulin like growth factor-I receptor expression and its clinico-pathological significance in histologic subtypes of human thyroid cancer. Experimental Biology and Medicine. 2009;234(4):372–386. [PubMed]
90. Wang Z, Chakravarty G, Kim S, et al. Growth-inhibitory effects of human anti-insulin-like growth factor-1 receptor antibody (A12) in an orthotopic nude mouse model of anaplastic thyroid carcinoma. Clinical Cancer Research. 2006;12(15):4755–4765. [PubMed]
91. Akslen LA, Varhaug JE. Oncoproteins and tumor progression in papillary thyroid carcinoma: presence of epidermal growth factor receptor, c-erbB-2 protein, estrogen receptor related protein, p21-ras protein, and proliferation indicators in relation to tumor recurrences and patient survival. Cancer. 1995;76(9):1643–1654. [PubMed]
92. Ness GO, Haugen DRF, Varhaug JE, Akslen LA, Lillehaug JR. Cytoplasmic localization of EGF receptor in papillary thyroid carcinomas: association with the 150-kDa receptor form. International Journal of Cancer. 1996;65(2):161–167. [PubMed]
93. Liu Z, Hou P, Ji M, et al. Highly prevalent genetic alterations in receptor tyrosine kinases and phosphatidylinositol 3-kinase/akt and mitogen-activated protein kinase pathways in anaplastic and follicular thyroid cancers. Journal of Clinical Endocrinology and Metabolism. 2008;93(8):3106–3116. [PubMed]
94. Vieira JM, Rosa Santos SC, Espadinha C, et al. Expression of vascular endothelial growth factor (VEGF) and its receptors in thyroid carcinomas of follicular origin: a potential autocrine loop. European Journal of Endocrinology. 2005;153(5):701–709. [PubMed]
95. Yegen G, Demir MA, Ertan Y, Nalbant OA, Tunçyürek M. Can CD10 be used as a diagnostic marker in thyroid pathology? Virchows Archiv. 2009;454(1):101–105. [PubMed]
96. Tomoda C, Kushima R, Takeuti E, Mukaisho K-I, Hattori T, Kitano H. CD10 expression is useful in the diagnosis of follicular carcinoma and follicular variant of papillary thyroid carcinoma. Thyroid. 2003;13(3):291–295. [PubMed]
97. Castellone MD, Guarino V, De Falco V, et al. Functional expression of the CXCR4 chemokine receptor is induced by RET/PTC oncogenes and is a common event in human papillary thyroid carcinomas. Oncogene. 2004;23(35):5958–5967. [PubMed]
98. Cerutti JM, Oler G, Michaluart P, Jr., et al. Molecular profiling of matched samples identifies biomarkers of papillary thyroid carcinoma lymph node metastasis. Cancer Research. 2007;67(16):7885–7892. [PubMed]
99. Takano T, Hasegawa Y, Matsuzuka F, et al. Gene expression profiles in thyroid carcinomas. British Journal of Cancer. 2000;83(11):1495–1502. [PMC free article] [PubMed]
100. Li D, Butt A, Clarke S, Swaminathan R. Real-time quantitative PCR measurement of thyroglobulin mRNA in peripheral blood of thyroid cancer patients and healthy subjects. Annals of the New York Academy of Sciences. 2004;1022:147–151. [PubMed]
101. Hesse E, Musholt PB, Potter E, et al. Oncofoetal fibronectin—a tumour-specific marker in detecting minimal residual disease in differentiated thyroid carcinoma. British Journal of Cancer. 2005;93(5):565–570. [PMC free article] [PubMed]
102. Nasr MR, Mukhopadhyay S, Zhang S, Katzenstein A-LA. Immunohistochemical markers in diagnosis of papillary thyroid carcinoma: utility of HBME1 combined with CK19 immunostaining. Modern Pathology. 2006;19(12):1631–1637. [PubMed]
103. Papotti M, Rodriguez J, De Pompa R, Bartolazzi A, Rosai J. Galectin-3 and HBME-1 expression in well-differentiated thyroid tumors with follicular architecture of uncertain malignant potential. Modern Pathology. 2004;18(4):541–546. [PubMed]
104. Ito Y, Yoshida H, Uruno T, et al. Survivin expression is significantly linked to the dedifferentiation of thyroid carcinoma. Oncology Reports. 2003;10(5):1337–1340. [PubMed]
105. Takano T, Ito Y, Matsuzuka F, et al. Quantitative measurement of telomerase reverse transcriptase, thyroglobulin and thyroid transcription factor 1 mRNAs in anaplastic thyroid carcinoma tissues and cell lines. Oncology Reports. 2007;18(3):715–720. [PubMed]
106. Umbricht CB, Conrad GT, Clark DP, et al. Human telomerase reverse transcriptase gene expression and the surgical management of suspicious thyroid tumors. Clinical Cancer Research. 2004;10(17):5762–5768. [PubMed]
107. Saji M, Xydas S, Westra WH, et al. Human telomerase reverse transcriptase (hTERT) gene expression in thyroid neoplasms. Clinical Cancer Research. 1999;5(6):1483–1489. [PubMed]
108. Wang S-L, Chen W-T, Wu M-T, Chan H-M, Yang S-F, Chai C-Y. Expression of human telomerase reverse transcriptase in thyroid follicular neoplasms: an immunohistochemical study. Endocrine Pathology. 2005;16(3):211–218. [PubMed]
109. Tan H, Ye K, Wang Z, Tang H. Clinicopathologic evaluation of immunohistochemical CD147 and MMP-2 expression in differentiated thyroid carcinoma. Japanese Journal of Clinical Oncology. 2008;38(8):528–533. [PubMed]
110. Cho MK, Eimoto T, Tateyama H, Arai Y, Fujiyoshi Y, Hamaguchi M. Expression of matrix metalloproteinases in benign and malignant follicular thyroid lesions. Histopathology. 2006;48(3):286–294. [PubMed]
111. Ito Y, Yoshida H, Kakudo K, Nakamura Y, Kuma K, Miyauchi A. Inverse relationships between the expression of MMP-7 and MMP-11 and predictors of poor prognosis of papillary thyroid carcinoma. Pathology. 2006;38(5):421–425. [PubMed]
112. Buergy D, Weber T, Maurer GD, et al. Urokinase receptor, MMP-1 and MMP-9 are markers to differentiate prognosis, adenoma and carcinoma in thyroid malignancies. International Journal of Cancer. 2009;125(4):894–901. [PubMed]
113. Sid B, Langlois B, Sartelet H, Bellon G, Dedieu S, Martiny L. Thrombospondin-1 enhances human thyroid carcinoma cell invasion through urokinase activity. International Journal of Biochemistry and Cell Biology. 2008;40(9):1890–1900. [PubMed]
114. Chen G, Zhang F-R, Ren J, et al. Expression of fascin in thyroid neoplasms: a novel diagnostic marker. Journal of Cancer Research and Clinical Oncology. 2008;134(9):947–951. [PubMed]
115. Kehlen A, Englert N, Seifert A, et al. Expression, regulation and function of autotaxin in thyroid carcinomas. International Journal of Cancer. 2004;109(6):833–838. [PubMed]
116. Seifert A, Klonisch T, Wulfaenger J, et al. The cellular localization of autotaxin impacts on its biological functions in human thyroid carcinoma cells. Oncology Reports. 2008;19(6):1485–1491. [PubMed]
117. Zito G, Richiusa P, Bommarito A, et al. In vitro identification and characterization of CD133pos cancer stem-like cells in anaplastic thyroid carcinoma cell lines. PLoS ONE. 2008;3(10, article e3544) [PMC free article] [PubMed]
118. Friedman S, Lu M, Schultz A, Thomas D, Lin R-Y. CD133+ anaplastic thyroid cancer cells initiate tumors in immunodeficient mice and are regulated by thyrotropin. PLoS ONE. 2009;4(4, article e5395) [PMC free article] [PubMed]
119. Maio M, Coral S, Sigalotti L, et al. Analysis of cancer/testis antigens in sporadic medullary thyroid carcinoma: expression and humoral response to NY-ESO-1. Journal of Clinical Endocrinology and Metabolism. 2003;88(2):748–754. [PubMed]
120. Wuttke M, Papewalis C, Jacobs B, Schott M. Identifying tumor antigens in endocrine malignancies. Trends in Endocrinology and Metabolism. 2009;20(3):122–129. [PubMed]
121. Uyttenhove C, Godfraind C, Lethé B, et al. The expression of mouse gene P1A in testis does not prevent safe induction of cytolytic T cells against a P1A-encoded tumor antigen. International Journal of Cancer. 1997;70(3):349–356. [PubMed]
122. Ciampolillo A, De Tullio C, Perlino E, Maiorano E. The IGF-I axis in thyroid carcinoma. Current Pharmaceutical Design. 2007;13(7):729–735. [PubMed]
123. Ciampolillo A, De Tullio C, Giorgino F. The IGF-I/IGF-I receptor pathway: implications in the pathophysiology of thyroid cancer. Current Medicinal Chemistry. 2005;12(24):2881–2891. [PubMed]
124. Mitsiades CS, Mitsiades NS, McMullan CJ, et al. Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors. Cancer Cell. 2004;5(3):221–230. [PubMed]
125. Lin J-D. Thyroglobulin and human thyroid cancer. Clinica Chimica Acta. 2008;388(1-2):15–21. [PubMed]
126. Tuttle RM, Leboeuf R, Martorella AJ. Papillary thyroid cancer: monitoring and therapy. Endocrinology and Metabolism Clinics of North America. 2007;36(3):753–778. [PubMed]
127. Rorive S, Eddafali B, Fernandez S, et al. Changes in galectin-7 and cytokeratin-19 expression during the progression of malignancy in thyroid tumors: diagnostic and biological implications. Modern Pathology. 2002;15(12):1294–1301. [PubMed]
128. Than TH, Swethadri GK, Wong J, et al. Expression of Galectin-3 and Galectin-7 in thyroid malignancy as potential diagnostic indicators. Singapore Medical Journal. 2008;49(4):333–338. [PubMed]
129. Giovanella L, Ceriani L, Ghelfo A, Maffioli M. Circulating cytokeratin 19 fragments in patients with benign nodules and carcinomas of the thyroid gland. International Journal of Biological Markers. 2008;23(1):54–57. [PubMed]
130. Califice S, Castronovo V, Van Den Brûle F. Galectin-3 and cancer (Review) International Journal of Oncology. 2004;25(4):983–992. [PubMed]
131. Hughes RC. Galectins as modulators of cell adhesion. Biochimie. 2001;83(7):667–676. [PubMed]
132. Honma I, Kitamura H, Torigoe T, et al. Phase I clinical study of anti-apoptosis protein survivin-derived peptide vaccination for patients with advanced or recurrent urothelial cancer. Cancer Immunology, Immunotherapy. 2009;58(11):1803–1809. [PubMed]
133. Croce M, Meazza R, Orengo AM, et al. Immunotherapy of neuroblastoma by an Interleukin-21-secreting cell vaccine involves survivin as antigen. Cancer Immunology, Immunotherapy. 2008;57(11):1625–1634. [PubMed]
134. Cho H-I, Kim E-K, Park S-Y, Lee SK, Hong Y-K, Kim T-G. Enhanced induction of anti-tumor immunity in human and mouse by dendritic cells pulsed with recombinant TAT fused human survivin protein. Cancer Letters. 2007;258(2):189–198. [PubMed]
135. Domchek SM, Recio A, Mick R, et al. Telomerase-specific T-cell immunity in breast cancer: effect of vaccination on tumor immunosurveillance. Cancer Research. 2007;67(21):10546–10555. [PubMed]
136. Mavroudis D, Bolonakis I, Cornet S, et al. A phase I study of the optimized cryptic peptide TERT(572Y) in patients with advanced malignancies. Oncology. 2006;70(4):306–314. [PubMed]
137. Vonderheide RH. Prospects and challenges of building a cancer vaccine targeting telomerase. Biochimie. 2008;90(1):173–180. [PMC free article] [PubMed]
138. Pasieka Z, Kuzdak K, Czyz W, Stepień H, Komorowski J. Soluble intracellular adhesion molecules (sICAM-1, sVCAM-1) in peripheral blood of patients with thyroid cancer. Neoplasma. 2004;51(1):34–37. [PubMed]
139. Komorowski J, Pasieka Z, Jankiewicz-Wika J, Stepień H. Matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases and angiogenic cytokines in peripheral blood of patients with thyroid cancer. Thyroid. 2002;12(8):655–662. [PubMed]
140. Yeh MW, Rougier J-P, Park J-W, et al. Differentiated thyroid cancer cell invasion is regulated through epidermal growth factor receptor-dependent activation of matrix metalloproteinase (MMP)-2/gelatinase A. Endocrine-Related Cancer. 2006;13(4):1173–1183. [PMC free article] [PubMed]
141. Rothhut B, Ghoneim C, Antonicelli F, Soula-Rothhut M. Epidermal growth factor stimulates matrix metalloproteinase-9 expression and invasion in human follicular thyroid carcinoma cells through Focal adhesion kinase. Biochimie. 2007;89(5):613–624. [PubMed]
142. Wiseman SM, Griffith OL, Deen S, et al. Identification of molecular markers altered during transformation of differentiated into anaplastic thyroid carcinoma. Archives of Surgery. 2007;142(8):717–727. [PubMed]
143. Wiseman SM, Melck A, Masoudi H, et al. Molecular phenotyping of thyroid tumors identifies a marker panel for differentiated thyroid cancer diagnosis. Annals of Surgical Oncology. 2008;15(10):2811–2826. [PubMed]
144. Broecker-Preuss M, Sheu S-Y, Worm K, et al. Expression and mutation analysis of the tyrosine kinase c-kit in poorly differentiated and anaplastic thyroid carcinoma. Hormone and Metabolic Research. 2008;40(10):685–691. [PubMed]
145. Dziba JM, Ain KB. Imatinib mesylate (Gleevec; STI571) monotherapy is ineffective in suppressing human anaplastic thyroid carcinoma cell growth in vitro. Journal of Clinical Endocrinology and Metabolism. 2004;89(5):2127–2135. [PubMed]
146. Mocellin S, Nitti D. Therapeutics targeting tumor immune escape: towards the development of new generation anticancer vaccines. Medicinal Research Reviews. 2008;28(3):413–444. [PubMed]
147. Frazier JL, Han JE, Lim M, Olivi A. Immunotherapy combined with chemotherapy in the treatment of tumors. Neurosurgery Clinics of North America. 2010;21(1):187–194. [PubMed]
148. Ramakrishnan R, Assudani D, Nagaraj S, et al. Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice. Journal of Clinical Investigation. 2010;120(4):1111–1124. [PMC free article] [PubMed]
149. Salem ML, Cole DJ. Dendritic cell recovery post-lymphodepletion: a potential mechanism for anti-cancer adoptive T cell therapy and vaccination. Cancer Immunology, Immunotherapy. 2010;59(3):341–353. [PMC free article] [PubMed]
150. Schlumberger M, Sherman SI. Clinical trials for progressive differentiated thyroid cancer: patient selection, study design, and recent advances. Thyroid. 2009;19(12):1393–1400. [PubMed]
151. Sherman SI, Wirth LJ, Droz J-P, et al. Motesanib diphosphate in progressive differentiated thyroid cancer. New England Journal of Medicine. 2008;359(1):31–42. [PubMed]
152. Wells SA, Jr., Gosnell JE, Gagel RF, et al. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. Journal of Clinical Oncology. 2010;28(5):767–772. [PMC free article] [PubMed]
153. Ozao-Choy J, Ge M, Kao J, et al. The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Research. 2009;69(6):2514–2522. [PMC free article] [PubMed]
154. Seggewiss R, Loré K, Greiner E, et al. Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner. Blood. 2005;105(6):2473–2479. [PubMed]
155. Abe F, Younos I, Westphal S, et al. Therapeutic activity of sunitinib for Her2/neu induced mammary cancer in FVB mice. International Immunopharmacology. 2010;10(1):140–145. [PubMed]
156. Borg C, Terme M, Taïeb J, et al. Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects. Journal of Clinical Investigation. 2004;114(3):379–388. [PMC free article] [PubMed]
157. Terme M, Ullrich E, Delahaye NF, Chaput N, Zitvogel L. Natural killer cell-directed therapies: moving from unexpected results to successful strategies. Nature Immunology. 2008;9(5):486–494. [PubMed]
158. Wolf D, Tilg H, Rumpold H, Gastl G, Wolf AM. The kinase inhibitor Imatinib—an immunosuppressive drug? Current Cancer Drug Targets. 2007;7(3):251–258. [PubMed]
159. van Cruijsen H, Van Der Veldt AAM, Vroling L, et al. Sunitinib-induced myeloid lineage redistribution in renal cell cancer patients: CD1c+ dendritic cell frequency predicts progression-free survival. Clinical Cancer Research. 2008;14(18):5884–5892. [PubMed]
160. Lissina A, Ladell K, Skowera A, et al. Protein kinase inhibitors substantially improve the physical detection of T-cells with peptide-MHC tetramers. Journal of Immunological Methods. 2009;340(1):11–24. [PMC free article] [PubMed]

Articles from Journal of Oncology are provided here courtesy of Hindawi