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Journal of Biomedicine and Biotechnology
Volume 2011 (2011), Article ID 918471, 19 pages
http://dx.doi.org/10.1155/2011/918471
Review Article

Tumor Evasion from T Cell Surveillance

1Section Experimental Neurosurgery/Tumor Immunology, Department of Neurosurgery, University Hospital Carl Gustav Carus, TU Dresden, Fetscherstraβe 74, 01307 Dresden, Germany
2Institute of Immunology, Medical Faculty Carl Gustav Carus, TU Dresden, Fetscherstraβe 74, 01307 Dresden, Germany

Received 31 May 2011; Accepted 29 August 2011

Academic Editor: Julie Curtsinger

Copyright © 2011 Katrin Töpfer et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. Ehrlich, “Über den jetzigen Stand der Karzinomforschung,” Nederlands Tijdschrift voor Geneeskunde, vol. 5, pp. 273–290, 1909.
  2. D. H. Kaplan, V. Shankaran, A. S. Dighe et al., “Demonstration of an interferon γ-dependent tumor surveillance system in immunocompetent mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 13, pp. 7556–7561, 1998. View at Publisher · View at Google Scholar · View at Scopus
  3. S. E. A. Street, J. A. Trapani, D. MacGregor, and M. J. Smyth, “Suppression of lymphoma and epithelial malignancies effected by interferon γ,” Journal of Experimental Medicine, vol. 196, no. 1, pp. 129–134, 2002. View at Publisher · View at Google Scholar · View at Scopus
  4. M. F. van den Broek, D. Kägi, F. Ossendorp et al., “Decreased tumor surveillance in perforin-deficient mice,” Journal of Experimental Medicine, vol. 184, no. 5, pp. 1781–1790, 1996. View at Scopus
  5. V. Shankaran, H. Ikeda, A. T. Bruce et al., “IFNγ, and lymphocytes prevent primary tumour development and shape tumour immunogenicity,” Nature, vol. 410, no. 6832, pp. 1107–1111, 2001. View at Publisher · View at Google Scholar · View at Scopus
  6. Y. Shinkai, G. Rathbun, K. P. Lam et al., “RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement,” Cell, vol. 68, no. 5, pp. 855–867, 1992. View at Publisher · View at Google Scholar · View at Scopus
  7. I. Penn, “Post-transplant malignancy. The role of immunosuppression,” Drug Safety, vol. 23, no. 2, pp. 101–113, 2000. View at Scopus
  8. M. Bower, C. Palmieri, and T. Dhillon, “AIDS-related malignancies: changing epidemiology and the impact of highly active antiretroviral therapy,” Current Opinion in Infectious Diseases, vol. 19, no. 1, pp. 14–19, 2006. View at Scopus
  9. N. Kayagaki, N. Yamaguchi, M. Nakayama, E. Hiroshi, K. Okumura, and H. Yagita, “Type I interferons (IFNs) regulate tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression on human T cells: a novel mechanism for the antitumor effects of type I IFNs,” Journal of Experimental Medicine, vol. 189, no. 9, pp. 1451–1460, 1999. View at Publisher · View at Google Scholar · View at Scopus
  10. I. Rousalova and E. Krepela, “Granzyme B-induced apoptosis in cancer cells and its regulation (review),” International Journal of Oncology, vol. 37, no. 6, pp. 1361–1378, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. R. F. Wang, “The role of MHC class II-restricted tumor antigens and CD4+ T cells in antitumor immunity,” Trends in Immunology, vol. 22, no. 5, pp. 269–276, 2001. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Cella, D. Scheidegger, K. Palmer-Lehmann, P. Lane, A. Lanzavecchia, and G. Alber, “Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation,” Journal of Experimental Medicine, vol. 184, no. 2, pp. 747–752, 1996. View at Scopus
  13. S. R. M. Clarke, “The critical role of CD40/CD40L in the CD4-dependent generation of CD8+ T cell immunity,” Journal of Leukocyte Biology, vol. 67, no. 5, pp. 607–614, 2000. View at Scopus
  14. C. Le Page, P. Génin, M. G. Baines, and J. Hiscott, “Interferon activation and innate immunity,” Reviews in Immunogenetics, vol. 2, no. 3, pp. 374–386, 2000. View at Scopus
  15. B. Seliger, F. Ruiz-Cabello, and F. Garrido, “Chapter 7 IFN inducibility of major histocompatibility antigens in tumors,” Advances in Cancer Research, vol. 101, pp. 249–276, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. R. D. Schreiber, L. J. Old, and M. J. Smyth, “Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion,” Science, vol. 331, no. 6024, pp. 1565–1570, 2011. View at Publisher · View at Google Scholar
  17. H. T. Khong and N. P. Restifo, “Natural selection of tumor variants in the generation of “tumor escape” phenotypes,” Nature Immunology, vol. 3, no. 11, pp. 999–1005, 2002. View at Publisher · View at Google Scholar · View at Scopus
  18. C. Palena and J. Schlom, “Vaccines against human carcinomas: strategies to improve antitumor immune responses,” Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 380697, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. C. Kurts, B. W. Robinson, and P. A. Knolle, “Cross-priming in health and disease,” Nature Reviews Immunology, vol. 10, pp. 403–414, 2010.
  20. P. Matzinger, “The danger model: a renewed sense of self,” Science, vol. 296, no. 5566, pp. 301–305, 2002. View at Publisher · View at Google Scholar · View at Scopus
  21. S. Burgdorf, C. Schölz, A. Kautz, R. Tampé, and C. Kurts, “Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation,” Nature Immunology, vol. 9, no. 5, pp. 558–566, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. T. Maurer, A. Heit, H. Hochrein et al., “CpG-DNA aided cross-presentation of soluble antigens by dendritic cells,” European Journal of Immunology, vol. 32, no. 8, pp. 2356–2364, 2002. View at Publisher · View at Google Scholar · View at Scopus
  23. O. Schulz, S. S. Diebold, M. Chen et al., “Toll-like receptor 3 promotes cross-priming to virus-infected cells,” Nature, vol. 433, no. 7028, pp. 887–892, 2005. View at Publisher · View at Google Scholar · View at Scopus
  24. H. Shen, B. M. Tesar, W. E. Walker, and D. R. Goldstein, “Dual signaling of MyD88 and TRIF is critical for maximal TLR4-induced dendritic cell maturation,” Journal of Immunology, vol. 181, no. 3, pp. 1849–1858, 2008. View at Scopus
  25. R. Barbalat, S. E. Ewald, M. L. Mouchess, and G. M. Barton, “Nucleic acid recognition by the innate immune system,” Annual Review of Immunology, vol. 29, pp. 185–214, 2011. View at Publisher · View at Google Scholar
  26. J. Tian, A. M. Avalos, S. Y. Mao et al., “Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE,” Nature Immunology, vol. 8, no. 5, pp. 487–496, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. R. Lande, J. Gregorio, V. Facchinetti et al., “Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide,” Nature, vol. 449, no. 7162, pp. 564–569, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Tesniere, F. Schlemmer, V. Boige et al., “Immunogenic death of colon cancer cells treated with oxaliplatin,” Oncogene, vol. 29, no. 4, pp. 482–491, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. P. Scaffidi, T. Misteli, and M. E. Bianchi, “Release of chromatin protein HMGB1 by necrotic cells triggers inflammation,” Nature, vol. 418, no. 6894, pp. 191–195, 2002. View at Publisher · View at Google Scholar · View at Scopus
  30. H. Yanai, T. Ban, Z. Wang et al., “HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses,” Nature, vol. 462, no. 7269, pp. 99–103, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. L. Apetoh, F. Ghiringhelli, A. Tesniere et al., “The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy,” Immunological Reviews, vol. 220, no. 1, pp. 47–59, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Kurts, H. Kosaka, F. R. Carbone, J. F. A. P. Miller, and W. R. Heath, “Class I-restricted cross-presentation of exogenous self-antigens leads to deletion of autoreactive CD8+ T cells,” Journal of Experimental Medicine, vol. 186, no. 2, pp. 239–245, 1997. View at Publisher · View at Google Scholar · View at Scopus
  33. A. J. Troy, K. L. Summers, P. J. T. Davidson, C. H. Atkinson, and D. N. J. Hart, “Minimal recruitment and activation of dendritic cells within renal cell carcinoma,” Clinical Cancer Research, vol. 4, no. 3, pp. 585–593, 1998. View at Scopus
  34. A. H. Enk, H. Jonuleit, J. Saloga, and J. Knop, “Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma,” International Journal of Cancer, vol. 73, no. 3, pp. 309–316, 1997. View at Publisher · View at Google Scholar · View at Scopus
  35. F. O. Nestle, G. Burg, J. Fäh, T. Wrone-Smith, and B. J. Nickoloff, “Human sunlight-induced basal-cell-carcinoma-associated dendritic cells are deficient in T cell co-stimulatory molecules and are impaired as antigen- presenting cells,” American Journal of Pathology, vol. 150, no. 2, pp. 641–651, 1997. View at Scopus
  36. D. I. Gabrilovich, J. Corak, I. F. Ciernik, D. Kavanaugh, and D. P. Carbone, “Decreased antigen presentation by dendritic cells in patients with breast cancer,” Clinical Cancer Research, vol. 3, no. 3, pp. 483–490, 1997. View at Scopus
  37. M. Stumpf, A. Hasenburg, M. O. Riener et al., “Intraepithelial CD8-positive T lymphocytes predict survival for patients with serous stage III ovarian carcinomas: relevance of clonal selection of T lymphocytes,” British Journal of Cancer, vol. 101, no. 9, pp. 1513–1521, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. K. R. Jerome, D. L. Barnd, K. M. Bendt et al., “Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by malignant cells,” Cancer Research, vol. 51, no. 11, pp. 2908–2916, 1991. View at Scopus
  39. C. N. Baxevanis, G. V. Z. Dedoussis, N. G. Papadopoulos, I. Missitzis, G. P. Stathopoulos, and M. Papamichail, “Tumor specific cytolysis by tumor infiltrating lymphocytes in breast cancer,” Cancer, vol. 74, no. 4, pp. 1275–1282, 1994. View at Publisher · View at Google Scholar · View at Scopus
  40. H. T. Khong, Q. J. Wang, and S. A. Rosenberg, “Identification of multiple antigens recognized by tumor-infiltrating lymphocytes from a single patient: tumor escape by antigen loss and loss of MHC expression,” Journal of Immunotherapy, vol. 27, no. 3, pp. 184–190, 2004. View at Scopus
  41. V. Deschoolmeester, M. Baay, E. Van Marck et al., “Tumor infiltrating lymphocytes: an intriguing player in the survival of colorectal cancer patients,” BMC Immunology, vol. 11, article 19, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Meissner, T. E. Reichert, M. Kunkel et al., “Defects in the human leukocyte antigen class I antigen-processing machinery in head and neck squamous cell carcinoma: association with clinical outcome,” Clinical Cancer Research, vol. 11, no. 7, pp. 2552–2560, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. Y. Nie, G. Y. Yang, Y. Song et al., “DNA hypermethylation is a mechanism for loss of expression of HLA class I genes in human esophageal squamous cell carcinomas,” Carcinogenesis, vol. 22, no. 10, pp. 1615–1623, 2001. View at Scopus
  44. P. Korkolopoulou, L. Kaklamanis, F. Pezzella, A. L. Harris, and K. C. Gatter, “Loss of antigen-presenting molecules (MHC class I and TAP-1) in lung cancer,” British Journal of Cancer, vol. 73, no. 2, pp. 148–153, 1996. View at Scopus
  45. M. G. Sanda, N. P. Restifo, J. C. Walsh et al., “Molecular characterization of defective antigen processing in human prostate cancer,” Journal of the National Cancer Institute, vol. 87, no. 4, pp. 280–285, 1995. View at Scopus
  46. I. Maleno, C. M. Cabrera, T. Cabrera et al., “Distribution of HLA class I altered phenotypes in colorectal carcinomas: high frequency of HLA haplotype loss associated with loss of heterozygosity in chromosome region 6p21,” Immunogenetics, vol. 56, no. 4, pp. 244–253, 2004. View at Scopus
  47. I. Maleno, J. M. Romero, T. Cabrera et al., “LOH at 6p21.3 region and HLA class altered phenotypes in bladder carcinomas,” Immunogenetics, vol. 58, no. 7, pp. 503–510, 2006. View at Publisher · View at Google Scholar · View at Scopus
  48. D. C. Bicknell, A. Rowan, and W. F. Bodmer, “β2-Microglobulin gene mutations: a study of established colorectal cell lines and fresh tumors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 11, pp. 4751–4755, 1994. View at Publisher · View at Google Scholar · View at Scopus
  49. D. J. Hicklin, Z. Wang, F. Arienti, L. Rivoltini, G. Parmiani, and S. Ferrone, “β2-Microglobulin mutations, HLA class I antigen loss, and tumor progression in melanoma,” Journal of Clinical Investigation, vol. 101, no. 12, pp. 2720–2729, 1998. View at Scopus
  50. E. Fonsatti, L. Sigalotti, S. Coral, F. Colizzi, M. Altomonte, and M. Maio, “Methylation-regulated expression of HLA class I antigens in melanoma,” International Journal of Cancer, vol. 105, no. 3, pp. 430–431, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. T. W. Soong and K. M. Hui, “Locus-specific transcriptional control of HLA genes,” Journal of Immunology, vol. 149, no. 6, pp. 2008–2020, 1992. View at Scopus
  52. J. Koch and R. Tampé, “The macromolecular peptide-loading complex in MHC class I-dependent antigen presentation,” Cellular and Molecular Life Sciences, vol. 63, no. 6, pp. 653–662, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Manning, M. Indrova, B. Lubyova et al., “Induction of MHC class I molecule cell surface expression and epigenetic activation of antigen-processing machinery components in a murine model for human papilloma virus 16-associated tumours,” Immunology, vol. 123, no. 2, pp. 218–227, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. B. Seliger, “Molecular mechanisms of MHC class I abnormalities and APM components in human tumors,” Cancer Immunology, Immunotherapy, vol. 57, no. 11, pp. 1719–1726, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. L. C. White, K. L. Wright, N. J. Felix et al., “Regulation of LMP2 and TAP1 genes by IRF-1 explains the paucity of CD8+ T cells in IRF-1(-/-) mice,” Immunity, vol. 5, no. 4, pp. 365–376, 1996. View at Publisher · View at Google Scholar · View at Scopus
  56. T. Rodríguez, R. Méndez, A. Del Campo et al., “Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines,” BMC Cancer, vol. 7, article 34, 2007. View at Publisher · View at Google Scholar · View at Scopus
  57. A. Respa, J. Bukur, S. Ferrone et al., “Association of IFN-γ signal transduction defects with impaired HLA class I antigen processing in melanoma cell lines,” Clinical Cancer Research, vol. 17, no. 9, pp. 2668–2678, 2011. View at Publisher · View at Google Scholar
  58. T. Hayashi, Y. Kobayashi, S. Kohsaka, and K. Sano, “The mutation in the ATP-binding region of JAK1, identified in human uterine leiomyosarcomas, results in defective interferon-γ inducibility of TAP1 and LMP2,” Oncogene, vol. 25, no. 29, pp. 4016–4026, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. M. Madhavan, P. Srinivas, E. Abraham, I. Ahmed, N. R. Vijayalekshmi, and P. Balaram, “Down regulation of endothelial adhesion molecules in node positive breast cancer: possible failure of host defence mechanism,” Pathology and Oncology Research, vol. 8, no. 2, pp. 125–128, 2002. View at Scopus
  60. L. Piali, A. Fichtel, H. J. Terpe, B. A. Imhof, and R. H. Gisler, “Endothelial vascular cell adhesion molecule 1 expression is suppressed by melanoma and carcinoma,” Journal of Experimental Medicine, vol. 181, no. 2, pp. 811–816, 1995. View at Publisher · View at Google Scholar · View at Scopus
  61. R. A. Clark, S. J. Huang, G. F. Murphy et al., “Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selectin and recruitment of regulatory T cells,” Journal of Experimental Medicine, vol. 205, no. 10, pp. 2221–2234, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. C. Weishaupt, K. N. Munoz, E. Buzney, T. S. Kupper, and R. C. Fuhlbrigge, “T-cell distribution and adhesion receptor expression in metastatic melanoma,” Clinical Cancer Research, vol. 13, no. 9, pp. 2549–2556, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. J. P. Medema, J. de Jong, L. T. C. Peltenburg et al., “Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 20, pp. 11515–11520, 2001. View at Publisher · View at Google Scholar · View at Scopus
  64. I. S. van Houdt, J. J. Oudejans, A. J. M. van den Eertwegh et al., “Expression of the apoptosis inhibitor protease inhibitor 9 predicts clinical outcome in vaccinated patients with stage III and IV melanoma,” Clinical Cancer Research, vol. 11, no. 17, pp. 6400–6407, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. Z. Mahmood and Y. Shukla, “Death receptors: targets for cancer therapy,” Experimental Cell Research, vol. 316, no. 6, pp. 887–899, 2010. View at Publisher · View at Google Scholar · View at Scopus
  66. T. S. Griffith, W. A. Chin, G. C. Jackson, D. H. Lynch, and M. Z. Kubin, “Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells,” Journal of Immunology, vol. 161, no. 6, pp. 2833–2840, 1998. View at Scopus
  67. C. Scaffidi, I. Schmitz, P. H. Krammer, and M. E. Peter, “The role of c-FLIP in modulation of CD95-induced apoptosis,” Journal of Biological Chemistry, vol. 274, no. 3, pp. 1541–1548, 1999. View at Publisher · View at Google Scholar · View at Scopus
  68. S. Y. Nam, G. A. Jung, G. C. Hur et al., “Upregulation of FLIPs by Akt, a possible inhibition mechanism of TRAIL-induced apoptosis in human gastric cancers,” Cancer Science, vol. 94, no. 12, pp. 1066–1073, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. A. Elnemr, T. Ohta, A. Yachie et al., “Human pancreatic cancer cells disable function of Fas receptors at several levels in Fas signal transduction pathway,” International Journal of Oncology, vol. 18, no. 2, pp. 311–316, 2001. View at Scopus
  70. C. W. Xiao, X. Yan, Y. Li, S. A. G. Reddy, and B. K. Tsang, “Resistance of human ovarian cancer cells to tumor necrosis factor α is a consequence of nuclear factor κB-mediated induction of Fas-associated death domain-like interleukin-1β-converting enzyme-like inhibitory protein,” Endocrinology, vol. 144, no. 2, pp. 623–630, 2003. View at Publisher · View at Google Scholar · View at Scopus
  71. X. Zhang, T. G. Jin, H. Yang, W. C. Dewolf, R. Khosravi-Far, and A. F. Olumi, “Persistent c-FLIP(L) expression is necessary and sufficient to maintain resistance to tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in prostate cancer,” Cancer Research, vol. 64, no. 19, pp. 7086–7091, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. G. J. Ullenhag, A. Mukherjee, N. F. S. Watson, A. H. Al-Attar, J. H. Scholefield, and L. G. Durrant, “Overexpression of FLIPL is an independent marker of poor prognosis in colorectal cancer patients,” Clinical Cancer Research, vol. 13, no. 17, pp. 5070–5075, 2007. View at Publisher · View at Google Scholar · View at Scopus
  73. J. Peli, M. Schröter, C. Rudaz et al., “Oncogenic Ras inhibits Fas ligand-mediated apoptosis by downregulating the expression of Fas,” EMBO Journal, vol. 18, no. 7, pp. 1824–1831, 1999. View at Scopus
  74. M. Volkmann, J. H. Schiff, Y. Hajjar et al., “Loss of CD95 expression is linked to most but not all p53 mutants in European hepatocellular carcinoma,” Journal of Molecular Medicine, vol. 79, no. 10, pp. 594–600, 2001. View at Publisher · View at Google Scholar · View at Scopus
  75. P. Moller, K. Koretz, F. Leithauser et al., “Expression of APO-1 (CD95), a member of the NGF/TNF receptor superfamily, in normal and neoplastic colon epithelium,” International Journal of Cancer, vol. 57, no. 3, pp. 371–377, 1994. View at Publisher · View at Google Scholar · View at Scopus
  76. T. H. Landowski, N. Qu, I. Buyuksal, J. S. Painter, and W. S. Dalton, “Mutations in the Fas antigen in patients with multiple myeloma,” Blood, vol. 90, no. 11, pp. 4266–4270, 1997. View at Scopus
  77. T. Maeda, Y. Yamada, R. Moriuchi et al., “Fas gene mutation in the progression of adult T cell leukemia,” Journal of Experimental Medicine, vol. 189, no. 7, pp. 1063–1071, 1999. View at Publisher · View at Google Scholar · View at Scopus
  78. W. S. Park, R. R. Oh, Y. S. Kim et al., “Somatic mutations in the death domain of the Fas (Apo-I/CD95) gene in gastric cancer,” Journal of Pathology, vol. 193, no. 2, pp. 162–168, 2001. View at Publisher · View at Google Scholar · View at Scopus
  79. M. S. Shin, H. S. Kim, S. H. Lee et al., “Mutations of tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2) genes in metastatic breast cancers,” Cancer Research, vol. 61, no. 13, pp. 4942–4946, 2001. View at Scopus
  80. J. Cheng, T. Zhou, C. Liu et al., “Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule,” Science, vol. 263, no. 5154, pp. 1759–1762, 1994. View at Scopus
  81. G. P. Midis, Y. Shen, and L. B. Owen-Schaub, “Elevated soluble Fas (sFas) levels in nonhematopoietic human malignancy,” Cancer Research, vol. 56, no. 17, pp. 3870–3874, 1996. View at Scopus
  82. S. Ugurel, G. Rappl, W. Tilgen, and U. Reinhold, “Increased soluble CD95 (sFas/CD95) serum level correlates with poor prognosis in melanoma patients,” Clinical Cancer Research, vol. 7, no. 5, pp. 1282–1286, 2001. View at Scopus
  83. R. M. Pitti, S. A. Marsters, D. A. Lawrence et al., “Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer,” Nature, vol. 396, no. 6712, pp. 699–703, 1998. View at Publisher · View at Google Scholar · View at Scopus
  84. W. Roth, S. Isenmann, M. Nakamura et al., “Soluble decoy receptor 3 is expressed by malignant gliomas and suppresses CD95 ligand-induced apoptosis and chemotaxis,” Cancer Research, vol. 61, no. 6, pp. 2759–2765, 2001. View at Scopus
  85. M. S. Sheikh, Y. Huang, E. A. Fernandez-Salas et al., “The antiapoptotic decoy receptor TRID/TRAIL-R3 is a p53-regulated DNA damage-inducible gene that is overexpressed in primary tumors of the gastrointestinal tract,” Oncogene, vol. 18, no. 28, pp. 4153–4159, 1999. View at Publisher · View at Google Scholar · View at Scopus
  86. R. D. Meng, E. R. McDonald III, M. S. Sheikh, A. J. Fornace Jr., and W. S. El-Deiry, “The TRAIL decoy receptor TRUNDD (DcR2, TRAIL-R4) is induced by adenovirus-p53 overexpression and can delay TRAIL-, p53-, and KILLER/DR5-dependent colon cancer apoptosis,” Molecular Therapy, vol. 1, no. 2, pp. 130–144, 2000. View at Publisher · View at Google Scholar · View at Scopus
  87. J. L. Fisher, R. J. Thomas-Mudge, J. Elliott et al., “Osteoprotegerin overexpression by breast cancer cells enhances orthotopic and osseous tumor growth and contrasts with that delivered therapeutically,” Cancer Research, vol. 66, no. 7, pp. 3620–3628, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. I. Holen, P. I. Croucher, F. C. Hamdy, and C. L. Eaton, “Osteoprotegerin (OPG) is a survival factor for human prostate cancer cells,” Cancer Research, vol. 62, no. 6, pp. 1619–1623, 2002. View at Scopus
  89. W. Zou and L. Chen, “Inhibitory B7-family molecules in the tumour microenvironment,” Nature Reviews Immunology, vol. 8, no. 6, pp. 467–477, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. A. V. Collins, D. W. Brodie, R. J. C. Gilbert et al., “The interaction properties of costimulatory molecules revisited,” Immunity, vol. 17, no. 2, pp. 201–210, 2002. View at Publisher · View at Google Scholar · View at Scopus
  91. R. V. Parry, J. M. Chemnitz, K. A. Frauwirth et al., “CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms,” Molecular and Cellular Biology, vol. 25, no. 21, pp. 9543–9553, 2005. View at Publisher · View at Google Scholar · View at Scopus
  92. F. S. Hodi, “Cytotoxic T-lymphocyte-associated antigen-4,” Clinical Cancer Research, vol. 13, no. 18, pp. 5238–5242, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. C. Blank, I. Brown, A. C. Peterson et al., “PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells,” Cancer Research, vol. 64, no. 3, pp. 1140–1145, 2004. View at Publisher · View at Google Scholar · View at Scopus
  94. J. Hamanishi, M. Mandai, M. Iwasaki et al., “Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 9, pp. 3360–3365, 2007. View at Publisher · View at Google Scholar · View at Scopus
  95. Y. Ohigashi, M. Sho, Y. Yamada et al., “Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer,” Clinical Cancer Research, vol. 11, no. 8, pp. 2947–2953, 2005. View at Publisher · View at Google Scholar · View at Scopus
  96. J. Nakanishi, Y. Wada, K. Matsumoto, M. Azuma, K. Kikuchi, and S. Ueda, “Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers,” Cancer Immunology, Immunotherapy, vol. 56, no. 8, pp. 1173–1182, 2007. View at Publisher · View at Google Scholar · View at Scopus
  97. J. Gadiot, A. I. Hooijkaas, A. D.M. Kaiser, H. Van Tinteren, H. Van Boven, and C. Blank, “Overall survival and PD-L1 expression in metastasized malignant melanoma,” Cancer, vol. 117, no. 10, pp. 2192–2201, 2011. View at Publisher · View at Google Scholar
  98. H. Dong, S. E. Strome, D. R. Salomao et al., “Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion,” Nature Medicine, vol. 8, no. 8, pp. 793–800, 2002. View at Publisher · View at Google Scholar · View at Scopus
  99. J. M. Chemnitz, R. V. Parry, K. E. Nichols, C. H. June, and J. L. Riley, “SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation,” Journal of Immunology, vol. 173, no. 2, pp. 945–954, 2004. View at Scopus
  100. X. Frigola, B. A. Inman, C. M. Lohse et al., “Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma,” Clinical Cancer Research, vol. 17, no. 7, pp. 1915–1923, 2011. View at Publisher · View at Google Scholar
  101. J. H. Kehrl, L. M. Wakefield, A. B. Roberts, et al., “Production of transforming growth factor β by human T lymphocytes and its potential role in the regulation of T cell growth,” Journal of Experimental Medicine, vol. 163, no. 5, pp. 1037–1050, 1986. View at Scopus
  102. G. E. Ranges, I. S. Figari, T. Espevik, and M. A. Palladino Jr., “Inhibition of cytotoxic T cell development by transforming growth factor β and reversal by recombinant tumor necrosis factor α,” Journal of Experimental Medicine, vol. 166, no. 4, pp. 991–998, 1987. View at Scopus
  103. H. Robson, E. Anderson, R. D. James, and P. F. Schofield, “Transforming growth factor β1 expression in human colorectal tumours: an independent prognostic marker in a subgroup of poor prognosis patients,” British Journal of Cancer, vol. 74, no. 5, pp. 753–758, 1996. View at Scopus
  104. B. H. A. von Rahden, H. J. Stein, M. Feith et al., “Overexpression of TGF-β1 in esophageal (Barrett's) adenocarcinoma is associated with advanced stage of disease and poor prognosis,” Molecular Carcinogenesis, vol. 45, no. 10, pp. 786–794, 2006. View at Publisher · View at Google Scholar · View at Scopus
  105. S. Bodmer, K. Strommer, K. Frei et al., “Immunosuppression and transforming growth factor-β in glioblastoma. Preferential production of transforming growth factor-β2,” Journal of Immunology, vol. 143, no. 10, pp. 3222–3229, 1989. View at Scopus
  106. R. A. Walker and S. J. Dearing, “Transforming growth factor beta1 in ductal carcinoma in situ and invasive carcinomas of the breast,” European Journal of Cancer, vol. 28, no. 2-3, pp. 641–644, 1992. View at Scopus
  107. Y. Hasegawa, S. Takanashi, Y. Kanehira, T. Tsushima, T. Imai, and K. Okumura, “Transforming growth factor-β1 level correlates with angiogenesis, tumor progression, and prognosis in patients with nonsmall cell lung carcinoma,” Cancer, vol. 91, no. 5, pp. 964–971, 2001. View at Scopus
  108. M. G. di Bari, M. E. Lutsiak, S. Takai et al., “TGF-beta modulates the functionality of tumor-infiltrating CD8+ T cells through effects on TCR signaling and Spred1 expression,” Cancer Immunology, Immunotherapy, vol. 58, no. 11, pp. 1809–1818, 2009. View at Publisher · View at Google Scholar · View at Scopus
  109. D. A. Thomas and J. Massagué, “TGF-β directly targets cytotoxic T cell functions during tumor evasion of immune surveillance,” Cancer Cell, vol. 8, no. 5, pp. 369–380, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. M. R. Walker, D. J. Kasprowicz, V. H. Gersuk et al., “Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells,” Journal of Clinical Investigation, vol. 112, no. 9, pp. 1437–1443, 2003. View at Publisher · View at Google Scholar · View at Scopus
  111. A. Greenhough, H. J. M. Smartt, A. E. Moore et al., “The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment,” Carcinogenesis, vol. 30, no. 3, pp. 377–386, 2009. View at Publisher · View at Google Scholar · View at Scopus
  112. B. A. Pockaj, G. D. Basu, L. B. Pathangey et al., “Reduced T-cell and dendritic cell function is related to cyclooxygenase-2 overexpression and prostaglandin E2 secretion in patients with breast cancer,” Annals of Surgical Oncology, vol. 11, no. 3, pp. 328–339, 2004. View at Publisher · View at Google Scholar · View at Scopus
  113. F. Baratelli, Y. Lin, L. Zhu et al., “Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells,” Journal of Immunology, vol. 175, no. 3, pp. 1483–1490, 2005. View at Scopus
  114. S. Sharma, L. Zhu, S. C. Yang et al., “Cyclooxygenase 2 inhibition promotes IFN-γ-dependent enhancement of antitumor responses,” Journal of Immunology, vol. 175, no. 2, pp. 813–819, 2005. View at Scopus
  115. L. Adams, G. K. Scott, and C. S. Weinberg, “Biphasic modulation of cell growth by recombinant human galectin-1,” Biochimica et Biophysica Acta—Molecular Cell Research, vol. 1312, no. 2, pp. 137–144, 1996. View at Publisher · View at Google Scholar · View at Scopus
  116. R. Matsumoto, H. Matsumoto, M. Seki et al., “Human ecalectin, a variant of human galectin-9, is a novel eosinophil chemoattractant produced by T lymphocytes,” Journal of Biological Chemistry, vol. 273, no. 27, pp. 16976–16984, 1998. View at Publisher · View at Google Scholar · View at Scopus
  117. K. Yamaoka, A. Ingendoh, S. Tsubuki, Y. Nagai, and Y. Sanai, “Structural and functional characterization of a novel tumor-derived rat galectin-1 having transforming growth factor (TGF) activity: the relationship between intramolecular disulfide bridges and TGF activity,” Journal of Biochemistry, vol. 119, no. 5, pp. 878–886, 1996. View at Scopus
  118. A. A. Mourad-Zeidan, V. O. Melnikova, H. Wang, A. Raz, and M. Bar-Eli, “Expression profiling of galectin-3-depleted melanoma cells reveals its major role in melanoma cell plasticity and vasculogenic mimicry,” American Journal of Pathology, vol. 173, no. 6, pp. 1839–1852, 2008. View at Publisher · View at Google Scholar · View at Scopus
  119. S. Rorive, N. Belot, C. Decaestecker et al., “Galectin-1 is highly expressed in human gliomas with relevance for modulation of invasion of tumor astrocytes into the brain parenchyma,” GLIA, vol. 33, no. 3, pp. 241–255, 2001. View at Publisher · View at Google Scholar · View at Scopus
  120. F. A. van den Brûle, D. Waltregny, and V. Castronovo, “Increased expression of galectin-I in carcinoma-associated stroma predicts poor outcome in prostate carcinoma patients,” Journal of Pathology, vol. 193, no. 1, pp. 80–87, 2001. View at Publisher · View at Google Scholar · View at Scopus
  121. L. Cindolo, G. Benvenuto, P. Salavatore et al., “Galectin-1 and galectin-3 expression in human bladder transitional-cell carcinomas,” International Journal of Cancer, vol. 84, no. 1, pp. 39–43, 1999. View at Publisher · View at Google Scholar · View at Scopus
  122. F. Van den Brûle, S. Califice, F. Garnier, P. L. Fernandez, A. Berchuck, and V. Castronovo, “Galectin-1 accumulation in the ovary carcinoma peritumoral stroma is induced by ovary carcinoma cells and affects both cancer cell proliferation and adhesion to laminin-1 and fibronectin,” Laboratory Investigation, vol. 83, no. 3, pp. 377–386, 2003.
  123. E. J. Jung, H. G. Moon, I. C. Bok et al., “Galectin-1 expression in cancer-associated stromal cells correlates tumor invasiveness and tumor progression in breast cancer,” International Journal of Cancer, vol. 120, no. 11, pp. 2331–2338, 2007. View at Publisher · View at Google Scholar · View at Scopus
  124. N. L. Perillo, K. E. Pace, J. J. Seilhamer, and L. G. Baum, “Apoptosis of T cells mediated by galectin-1,” Nature, vol. 378, no. 6558, pp. 736–739, 1995. View at Scopus
  125. G. A. Rabinovich, M. M. Iglesias, N. M. Modesti et al., “Activated rat macrophages produce a galectin-1-like protein that induces apoptosis of T cells: biochemical and functional characterization,” Journal of Immunology, vol. 160, no. 10, pp. 4831–4840, 1998. View at Scopus
  126. C. D. Chung, V. P. Patel, M. Moran, L. A. Lewis, and M. C. Miceli, “Galectin-1 induces partial TCR ζ-chain phosphorylation and antagonizes processive TCR signal transduction,” Journal of Immunology, vol. 165, no. 7, pp. 3722–3729, 2000. View at Scopus
  127. D. R. Green, N. Droin, and M. Pinkoski, “Activation-induced cell death in T cells,” Immunological Reviews, vol. 193, pp. 70–81, 2003. View at Publisher · View at Google Scholar
  128. M. Hahne, D. Rimoldi, M. Schröter et al., “Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape,” Science, vol. 274, no. 5291, pp. 1363–1366, 1996. View at Publisher · View at Google Scholar · View at Scopus
  129. G. A. Niehans, T. Brunner, S. P. Frizelle et al., “Human lung carcinomas express Fas ligand,” Cancer Research, vol. 57, no. 6, pp. 1007–1012, 1997. View at Scopus
  130. W. V. Bernstorff, J. N. Glickman, R. D. Odze et al., “Fas (CD95/APO-1) and Fas ligand expression in normal pancreas and pancreatic tumors: implications for immune privilege and immune escape,” Cancer, vol. 94, no. 10, pp. 2552–2560, 2002. View at Publisher · View at Google Scholar · View at Scopus
  131. L. Müllauer, I. Mosberger, M. Grusch, M. Rudas, and A. Chott, “Fas ligand is expressed in normal breast epithelial cells and is frequently up-regulated in breast cancer,” Journal of Pathology, vol. 190, no. 1, pp. 20–30, 2000. View at Publisher · View at Google Scholar · View at Scopus
  132. H. Arai, D. Gordon, E. G. Nabel, and G. J. Nabel, “Gene transfer of Fas ligand induces tumor regression in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 25, pp. 13862–13867, 1997. View at Publisher · View at Google Scholar · View at Scopus
  133. S. M. Kang, Z. Lin, N. L. Ascher, and P. G. Stock, “Fas ligand expression on islets as well as multiple cell lines results in accelerated neutrophilic rejection,” Transplantation Proceedings, vol. 30, no. 2, p. 538, 1998. View at Publisher · View at Google Scholar · View at Scopus
  134. M. Drozdzik, C. Qian, J. J. Lasarte, R. Bilbao, and J. Prieto, “Antitumor effect of allogenic fibroblasts engineered to express Fas ligand (FasL),” Gene Therapy, vol. 5, no. 12, pp. 1622–1630, 1998. View at Scopus
  135. A. E. Ryan, F. Shanahan, J. O'Connell, and A. M. Houston, “Addressing the "Fas counterattack" controversy: blocking fas ligand expression suppresses tumor immune evasion of colon cancer in vivo,” Cancer Research, vol. 65, no. 21, pp. 9817–9823, 2005. View at Publisher · View at Google Scholar · View at Scopus
  136. G. Andreola, L. Rivoltini, C. Castelli et al., “Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles,” Journal of Experimental Medicine, vol. 195, no. 10, pp. 1303–1316, 2002. View at Publisher · View at Google Scholar · View at Scopus
  137. M. Iero, R. Valenti, V. Huber et al., “Tumour-released exosomes and their implications in cancer immunity,” Cell Death and Differentiation, vol. 15, no. 1, pp. 80–88, 2008. View at Publisher · View at Google Scholar · View at Scopus
  138. K. Shiraki, T. Yamanaka, H. Inoue et al., “Expression of TNF-related apoptosis-inducing ligand in human hepatocellular carcinoma,” International Journal of Oncology, vol. 26, no. 5, pp. 1273–1281, 2005. View at Scopus
  139. D. H. Munn, M. Zhou, J. T. Attwood et al., “Prevention of allogeneic fetal rejection by tryptophan catabolism,” Science, vol. 281, no. 5380, pp. 1191–1193, 1998. View at Scopus
  140. G. Frumento, R. Rotondo, M. Tonetti, G. Damonte, U. Benatti, and G. B. Ferrara, “Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase,” Journal of Experimental Medicine, vol. 196, no. 4, pp. 459–468, 2002. View at Publisher · View at Google Scholar · View at Scopus
  141. S. Löb, A. Königsrainer, D. Zieker et al., “IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism,” Cancer Immunology, Immunotherapy, vol. 58, no. 1, pp. 153–157, 2009. View at Publisher · View at Google Scholar · View at Scopus
  142. S. Sakaguchi, M. Ono, R. Setoguchi et al., “Foxp3+CD25+CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease,” Immunological Reviews, vol. 212, pp. 8–27, 2006. View at Publisher · View at Google Scholar · View at Scopus
  143. B. T. Fife and J. A. Bluestone, “Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways,” Immunological Reviews, vol. 224, no. 1, pp. 166–182, 2008. View at Publisher · View at Google Scholar · View at Scopus
  144. S. Hori, T. Nomura, and S. Sakaguchi, “Control of regulatory T cell development by the transcription factor Foxp3,” Science, vol. 299, no. 5609, pp. 1057–1061, 2003. View at Publisher · View at Google Scholar · View at Scopus
  145. C. Schaefer, G. G. Kim, A. Albers, K. Hoermann, E. N. Myers, and T. L. Whiteside, “Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer,” British Journal of Cancer, vol. 92, no. 5, pp. 913–920, 2005. View at Publisher · View at Google Scholar · View at Scopus
  146. A. M. Wolf, D. Wolf, M. Steurer, G. Gastl, E. Gunsilius, and B. Grubeck-Loebenstein, “Increase of regulatory T cells in the peripheral blood of cancer patients,” Clinical Cancer Research, vol. 9, no. 2, pp. 606–612, 2003. View at Scopus
  147. J. R. Yannelli, J. A. Tucker, G. Hidalgo, S. Perkins, R. Kryscio, and E. A. Hirschowitz, “Characteristics of PBMC obtained from leukapheresis products and tumor biopsies of patients with non-small cell lung cancer,” Oncology Reports, vol. 22, no. 6, pp. 1459–1471, 2009. View at Publisher · View at Google Scholar · View at Scopus
  148. N. Hiraoka, K. Onozato, T. Kosuge, and S. Hirohashi, “Prevalence of Foxp3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions,” Clinical Cancer Research, vol. 12, no. 18, pp. 5423–5434, 2006. View at Publisher · View at Google Scholar · View at Scopus
  149. S. A. Perez, M. V. Karamouzis, D. V. Skarlos et al., “CD4+CD25+ regulatory T-cell frequency in HER-2/neu (HER)-positive and HER-negative advanced-stage breast cancer patients,” Clinical Cancer Research, vol. 13, no. 9, pp. 2714–2721, 2007. View at Publisher · View at Google Scholar · View at Scopus
  150. L. Ormandy, T. Hillemann, H. Wedemeyer, M. P. Manns, T. F. Greten, and F. Korangy, “Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma,” Cancer Research, vol. 65, no. 6, pp. 2457–2464, 2005. View at Publisher · View at Google Scholar · View at Scopus
  151. T. J. Curiel, G. Coukos, L. Zou et al., “Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival,” Nature Medicine, vol. 10, no. 9, pp. 942–949, 2004. View at Publisher · View at Google Scholar · View at Scopus
  152. F. Ichihara, K. Kono, A. Takahashi, H. Kawaida, H. Sugai, and H. Fujii, “Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers,” Clinical Cancer Research, vol. 9, no. 12, pp. 4404–4408, 2003. View at Scopus
  153. M. Viguier, F. Lemaître, O. Verola et al., “Foxp3 expressing CD4+CD25high regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells,” Journal of Immunology, vol. 173, no. 2, pp. 1444–1453, 2004. View at Scopus
  154. N. Kobayashi, N. Hiraoka, W. Yamagami et al., “Foxp3+ regulatory T cells affect the development and progression of hepatocarcinogenesis,” Clinical Cancer Research, vol. 13, no. 3, pp. 902–911, 2007. View at Publisher · View at Google Scholar · View at Scopus
  155. T. Ishida, T. Ishii, A. Inagaki et al., “Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege,” Cancer Research, vol. 66, no. 11, pp. 5716–5722, 2006. View at Publisher · View at Google Scholar · View at Scopus
  156. B. Almand, J. R. Resser, B. Lindman et al., “Clinical significance of defective dendritic cell differentiation in cancer,” Clinical Cancer Research, vol. 6, no. 5, pp. 1755–1766, 2000. View at Scopus
  157. P. C. Rodriguez, C. P. Hernandez, K. Morrow et al., “L-arginine deprivation regulates cyclin D3 mRNA stability in human T cells by controlling HuR expression,” Journal of Immunology, vol. 185, no. 9, pp. 5198–5204, 2010. View at Publisher · View at Google Scholar · View at Scopus
  158. J. Schmielau and O. J. Finn, “Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of T-cell function in advanced cancer patients,” Cancer Research, vol. 61, no. 12, pp. 4756–4760, 2001. View at Scopus
  159. M. M. Mueller and N. E. Fusenig, “Constitutive expression of G-CSF and GM-CSF in human skin carcinoma cells with functional consequence for tumor progression,” International Journal of Cancer, vol. 83, no. 6, pp. 780–789, 1999. View at Publisher · View at Google Scholar · View at Scopus
  160. N. Rochet, J. Dubousset, C. Mazeau et al., “Establishment, characterisation and partial cytokine expression profile of a new human osteosarcoma cell line (CAL 72),” International Journal of Cancer, vol. 82, no. 2, pp. 282–285, 1999. View at Publisher · View at Google Scholar · View at Scopus
  161. M. Wislez, J. Fleury-Feith, N. Rabbe et al., “Tumor-derived granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor prolong the survival of neutrophils infiltrating bronchoalveolar subtype pulmonary adenocarcinoma,” American Journal of Pathology, vol. 159, no. 4, pp. 1423–1433, 2001. View at Scopus
  162. V. Bronte, D. B. Chappell, E. Apolloni et al., “Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8+ T cell responses by dysregulating antigen-presenting cell maturation,” Journal of Immunology, vol. 162, no. 10, pp. 5728–5737, 1999. View at Scopus
  163. S. Nagaraj, K. Gupta, V. Pisarev et al., “Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer,” Nature Medicine, vol. 13, no. 7, pp. 828–835, 2007. View at Publisher · View at Google Scholar · View at Scopus
  164. S. Tuyaerts, J. L. Aerts, J. Corthals et al., “Current approaches in dendritic cell generation and future implications for cancer immunotherapy,” Cancer Immunology, Immunotherapy, vol. 56, no. 10, pp. 1513–1537, 2007. View at Publisher · View at Google Scholar · View at Scopus
  165. L. Yang and D. P. Carbone, “Tumor-host immune interactions and dendritic cell dysfunction,” Advances in Cancer Research, vol. 92, pp. 13–27, 2004. View at Publisher · View at Google Scholar · View at Scopus
  166. B. G. Molenkamp, B. J. R. Sluijter, P. A. M. Van Leeuwen et al., “Local administration of PF-3512676 CpG-B instigates tumor-specific CD8+ T-cell reactivity in melanoma patients,” Clinical Cancer Research, vol. 14, no. 14, pp. 4532–4542, 2008. View at Publisher · View at Google Scholar · View at Scopus
  167. E. Papadavid, A. J. Stratigos, and M. E. Falagas, “Imiquimod: an immune response modifier in the treatment of precancerous skin lesions and skin cancer,” Expert Opinion on Pharmacotherapy, vol. 8, no. 11, pp. 1743–1755, 2007. View at Publisher · View at Google Scholar · View at Scopus
  168. R. M. Prins, H. Soto, V. Konkankit et al., “Gene expression profile correlates with T-cell infiltration and relative survival in glioblastoma patients vaccinated with dendritic cell immunotherapy,” Clinical Cancer Research, vol. 17, no. 6, pp. 1603–1615, 2011. View at Publisher · View at Google Scholar
  169. L. G. Di, C. Buonerba, and P. W. Kantoff, “Immunotherapy for the treatment of prostate cancer,” Nature Reviews Clinical Oncology, vol. 8, pp. 551–561, 2011.
  170. F. Foss, “Clinical experience with denileukin diftitox (ONTAK),” Seminars in Oncology, vol. 33, no. 3, pp. S11–S16, 2006. View at Publisher · View at Google Scholar · View at Scopus
  171. M. A. Morse, A. C. Hobeika, T. Osada et al., “Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines,” Blood, vol. 112, no. 3, pp. 610–618, 2008. View at Publisher · View at Google Scholar · View at Scopus
  172. C. H. June, “Principles of adoptive T cell cancer therapy,” Journal of Clinical Investigation, vol. 117, no. 5, pp. 1204–1212, 2007. View at Publisher · View at Google Scholar · View at Scopus
  173. M. E. Dudley, J. Wunderlich, M. I. Nishimura et al., “Adoptive transfer of cloned melanoma-reactive T lymphocytes for the treatment of patients with metastatic melanoma,” Journal of Immunotherapy, vol. 24, no. 4, pp. 363–373, 2001. View at Publisher · View at Google Scholar · View at Scopus
  174. M. E. Dudley, J. R. Wunderlich, J. C. Yang et al., “Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma,” Journal of Clinical Oncology, vol. 23, no. 10, pp. 2346–2357, 2005. View at Publisher · View at Google Scholar · View at Scopus
  175. M. E. Dudley, J. R. Wunderlich, P. F. Robbins et al., “Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes,” Science, vol. 298, no. 5594, pp. 850–854, 2002. View at Publisher · View at Google Scholar · View at Scopus
  176. S. A. Rosenberg, J. C. Yang, R. M. Sherry, et al., “Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy,” Clinical Cancer Research, vol. 17, pp. 4550–4557, 2011.
  177. K. S. Peggs, S. A. Quezada, A. J. Korman, and J. P. Allison, “Principles and use of anti-CTLA4 antibody in human cancer immunotherapy,” Current Opinion in Immunology, vol. 18, no. 2, pp. 206–213, 2006. View at Publisher · View at Google Scholar · View at Scopus
  178. Y. Iwai, M. Ishida, Y. Tanaka, T. Okazaki, T. Honjo, and N. Minato, “Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 19, pp. 12293–12297, 2002. View at Publisher · View at Google Scholar · View at Scopus
  179. J. R. Brahmer, C. G. Drake, I. Wollner et al., “Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates,” Journal of Clinical Oncology, vol. 28, no. 19, pp. 3167–3175, 2010. View at Publisher · View at Google Scholar · View at Scopus
  180. E. D. Kwon, B. A. Foster, A. A. Hurwitz et al., “Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade immunotherapy,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 26, pp. 15074–15079, 1999. View at Publisher · View at Google Scholar · View at Scopus
  181. D. R. Leach, M. F. Krummel, and J. P. Allison, “Enhancement of antitumor immunity by CTLA-4 blockade,” Science, vol. 271, no. 5256, pp. 1734–1736, 1996. View at Scopus
  182. A. A. Sarnaik and J. S. Weber, “Recent advances using anti-CTLA-4 for the treatment of melanoma,” Cancer Journal, vol. 15, no. 3, pp. 169–173, 2009. View at Publisher · View at Google Scholar · View at Scopus
  183. J. A. Blansfield, K. E. Beck, K. Tran et al., “Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer,” Journal of Immunotherapy, vol. 28, no. 6, pp. 593–598, 2005. View at Scopus
  184. K. E. Beck, J. A. Blansfield, K. Q. Tran et al., “Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4,” Journal of Clinical Oncology, vol. 24, no. 15, pp. 2283–2289, 2006. View at Publisher · View at Google Scholar · View at Scopus
  185. F. S. Hodi, S. J. O'Day, D. F. McDermott et al., “Improved survival with ipilimumab in patients with metastatic melanoma,” New England Journal of Medicine, vol. 363, no. 8, pp. 711–723, 2010. View at Publisher · View at Google Scholar · View at Scopus
  186. H. W. Lee, S. J. Park, B. K. Choi, H. H. Kim, K. O. Nam, and B. S. Kwon, “4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1,” Journal of Immunology, vol. 169, no. 9, pp. 4882–4888, 2002. View at Scopus
  187. L. Stärck, C. Scholz, B. Dörken, and P. T. Daniel, “Costimulation by CD137/4-1BB inhibits T cell apoptosis and induces Bcl-xL and c-FLIPshort via phosphatidylinositol 3-kinase and AKT/protein kinase B,” European Journal of Immunology, vol. 35, no. 4, pp. 1257–1266, 2005. View at Publisher · View at Google Scholar · View at Scopus
  188. A. Tomillero and M. A. Moral, “Gateways to clinical trials,” Methods and Findings in Experimental and Clinical Pharmacology, vol. 30, no. 7, pp. 543–588, 2008.
  189. M. Croft, “Control of immunity by the TNFR-related molecule OX40 (CD134),” Annual Review of Immunology, vol. 28, pp. 57–78, 2010. View at Publisher · View at Google Scholar · View at Scopus
  190. A. D. Weinberg, M. M. Rivera, R. Prell et al., “Engagement of the OX-40 receptor in vivo enhances antitumor immunity,” Journal of Immunology, vol. 164, no. 4, pp. 2160–2169, 2000. View at Scopus
  191. J. F. M. Jacobs, C. J. A. Punt, W. J. Lesterhuis et al., “Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I/II study in metastatic melanoma patients,” Clinical Cancer Research, vol. 16, no. 20, pp. 5067–5078, 2010. View at Publisher · View at Google Scholar · View at Scopus
  192. D. Coe, S. Begom, C. Addey, M. White, J. Dyson, and J. G. Chai, “Depletion of regulatory T cells by anti-GITR mAb as a novel mechanism for cancer immunotherapy,” Cancer Immunology, Immunotherapy, vol. 59, no. 9, pp. 1367–1377, 2010. View at Publisher · View at Google Scholar · View at Scopus
  193. K. W. Moore, M. R. de Waal, R. L. Coffman, and A. O'Garra, “Interleukin-10 and the interleukin-10 receptor,” Annual Review of Immunology, vol. 19, pp. 683–765, 2001.
  194. P. Hau, P. Jachimczak, R. Schlingensiepen et al., “Inhibition of TGF-β2 with ap 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies,” Oligonucleotides, vol. 17, no. 2, pp. 201–212, 2007. View at Publisher · View at Google Scholar · View at Scopus
  195. U. Bogdahn, P. Hau, G. Stockhammer et al., “Targeted therapy for high-grade glioma with the TGF-β2 inhibitor trabedersen: results of a randomized and controlled phase IIb study,” Neuro-Oncology, vol. 13, no. 1, pp. 132–142, 2011. View at Publisher · View at Google Scholar
  196. P. DeLong, T. Tanaka, R. Kruklitis et al., “Use of cyclooxygenase-2 inhibition to enhance the efficacy of immunotherapy,” Cancer Research, vol. 63, no. 22, pp. 7845–7852, 2003. View at Scopus
  197. R. A. Morgan, M. E. Dudley, J. R. Wunderlich et al., “Cancer regression in patients after transfer of genetically engineered lymphocytes,” Science, vol. 314, no. 5796, pp. 126–129, 2006. View at Publisher · View at Google Scholar · View at Scopus
  198. L. A. Johnson, R. A. Morgan, M. E. Dudley et al., “Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen,” Blood, vol. 114, no. 3, pp. 535–546, 2009. View at Publisher · View at Google Scholar · View at Scopus
  199. Z. Eshhar, T. Waks, G. Gross, and D. G. Schindler, “Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the γ or ζ subunits of the immunoglobulin and T-cell receptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 2, pp. 720–724, 1993. View at Publisher · View at Google Scholar · View at Scopus
  200. M. Bachmann, M. Cartellieri, A. Feldmann et al., “Chimeric antigen receptor-engineered T cells for immunotherapy of cancer,” Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 956304, 2010. View at Publisher · View at Google Scholar · View at Scopus
  201. J. R. Park, D. L. DiGiusto, M. Slovak et al., “Adoptive transfer of chimeric antigen receptor re-directed cytolytic T lymphocyte clones in patients with neuroblastoma,” Molecular Therapy, vol. 15, no. 4, pp. 825–833, 2007. View at Publisher · View at Google Scholar · View at Scopus
  202. B. G. Till, M. C. Jensen, J. Wang et al., “Adoptive immunotherapy for indolent non-hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells,” Blood, vol. 112, no. 6, pp. 2261–2271, 2008. View at Publisher · View at Google Scholar · View at Scopus
  203. J. N. Kochenderfer, W. H. Wilson, J. E. Janik et al., “Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19,” Blood, vol. 116, no. 20, pp. 4099–4102, 2010. View at Publisher · View at Google Scholar · View at Scopus
  204. A. Hombach, D. Sent, C. Schneider et al., “T-cell activation by recombinant receptors: CD28 costimulation is required for interleukin 2 secretion and receptor-mediated T-cell proliferation but does not affect receptor-mediated target cell lysis,” Cancer Research, vol. 61, no. 5, pp. 1976–1982, 2001. View at Scopus
  205. M. A. Pulè, K. C. Straathof, G. Dotti, H. E. Heslop, C. M. Rooney, and M. K. Brenner, “A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells,” Molecular Therapy, vol. 12, no. 5, pp. 933–941, 2005. View at Publisher · View at Google Scholar · View at Scopus
  206. Y. Zhao, Q. J. Wang, S. Yang et al., “A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity,” Journal of Immunology, vol. 183, no. 9, pp. 5563–5574, 2009. View at Publisher · View at Google Scholar · View at Scopus
  207. K. Liu and S. A. Rosenberg, “Transduction of an IL-2 gene into human melanoma-reactive lymphocytes results in their continued growth in the absence of exogenous IL-2 and maintenance of specific antitumor activity,” Journal of Immunology, vol. 167, no. 11, pp. 6356–6365, 2001. View at Scopus
  208. J. Charo, S. E. Finkelstein, N. Grewal, N. P. Restifo, P. F. Robbins, and S. A. Rosenberg, “Bcl-2 overexpression enhances tumor-specific T-cell survival,” Cancer Research, vol. 65, no. 5, pp. 2001–2008, 2005. View at Publisher · View at Google Scholar · View at Scopus
  209. A. Di Stasi, B. De Angelis, C. M. Rooney et al., “T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model,” Blood, vol. 113, no. 25, pp. 6392–6402, 2009. View at Publisher · View at Google Scholar · View at Scopus
  210. J. S. Yu, G. Liu, H. Ying, W. H. Yong, K. L. Black, and C. J. Wheeler, “Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma,” Cancer Research, vol. 64, no. 14, pp. 4973–4979, 2004. View at Publisher · View at Google Scholar · View at Scopus
  211. P. M. Arlen, M. Pazdur, L. Skarupa, M. Rauckhorst, and J. L. Gulley, “A ramdomized phase II study of docetaxel alone or in combination with PANVAC-V (Vaccinia) and PANVAC-F (Fowlpox) in patients with metastatic breast cancer (NCI 05-C-0229),” Clinical Breast Cancer, vol. 7, no. 2, pp. 176–179, 2006. View at Publisher · View at Google Scholar · View at Scopus
  212. S. Oh, M. Terabe, C. D. Pendleton et al., “Human CTLs to wild-type and enhanced epitopes of a novel prostate and breast tumor-associated protein, TARP, lyse human breast cancer cells,” Cancer Research, vol. 64, no. 7, pp. 2610–2618, 2004. View at Publisher · View at Google Scholar · View at Scopus
  213. J. M. Kirkwood, S. Lee, S. Moschos et al., “Immunogenicity and antitumor effects of vaccination with peptide vaccine +/- granulocyte-monocyte colony-stimulating factor and/or IFIN-α2b in advanced metastatic melanoma: eastern cooperative oncology group phase II trial E1696,” Clinical Cancer Research, vol. 15, no. 4, pp. 1443–1451, 2009. View at Publisher · View at Google Scholar · View at Scopus
  214. K. Sanderson, R. Scotland, P. Lee et al., “Autoimmunity in a phase I trial of a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody with multiple melanoma peptides and montanide ISA 51 for patients with resected stages III and IV melanoma,” Journal of Clinical Oncology, vol. 23, no. 4, pp. 741–750, 2005. View at Publisher · View at Google Scholar · View at Scopus
  215. R. F. Rousseau, E. Biagi, A. Dutour et al., “Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation,” Blood, vol. 107, no. 4, pp. 1332–1341, 2006. View at Publisher · View at Google Scholar · View at Scopus
  216. E. Atchison, J. Eklund, B. Martone et al., “A pilot study of denileukin diftitox (DD) in combination with high-dose interleukin-2 (IL-2) for patients with metastatic renal cell carcinoma (RCC),” Journal of Immunotherapy, vol. 33, no. 7, pp. 716–722, 2010. View at Publisher · View at Google Scholar · View at Scopus