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Journal of Biomedicine and Biotechnology
Volume 2010, Article ID 380697, 12 pages
http://dx.doi.org/10.1155/2010/380697
Review Article

Vaccines against Human Carcinomas: Strategies to Improve Antitumor Immune Responses

Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

Received 7 December 2009; Accepted 8 January 2010

Academic Editor: Zhengguo Xiao

Copyright © 2010 Claudia Palena and Jeffrey Schlom. 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. G. P. Dunn, A. T. Bruce, H. Ikeda, L. J. Old, and R. D. Schreiber, “Cancer immunoediting: from immunosurveillance to tumor escape,” Nature Immunology, vol. 3, no. 11, pp. 991–998, 2002. View at Publisher · View at Google Scholar · View at PubMed
  2. 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 PubMed
  3. M. Girardi, E. Glusac, R. B. Filler et al., “The distinct contributions of murine T cell receptor (TCR)γδ+ and TCRαβ+ T cells to different stages of chemically induced skin cancer,” Journal of Experimental Medicine, vol. 198, no. 5, pp. 747–755, 2003. View at Publisher · View at Google Scholar · View at PubMed
  4. M. J. Smyth, K. Y. T. Thia, S. E. A. Street et al., “Differential tumor surveillance by natural killer (NK) and NKT cells,” Journal of Experimental Medicine, vol. 191, no. 4, pp. 661–668, 2000. View at Publisher · View at Google Scholar
  5. M. E. van den Broek, D. Kagi, 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 Google Scholar
  6. F. Pages, A. Berger, M. Camus et al., “Effector memory T cells, early metastasis, and survival in colorectal cancer,” The New England Journal of Medicine, vol. 353, no. 25, pp. 2654–2666, 2005. View at Publisher · View at Google Scholar · View at PubMed
  7. J. Galon, A. Costes, F. Sanchez-Cabo et al., “Type, density, and location of immune cells within human colorectal tumors predict clinical outcome,” Science, vol. 313, no. 5795, pp. 1960–1964, 2006. View at Publisher · View at Google Scholar · View at PubMed
  8. S. J. Piersma, E. S. Jordanova, M. I. E. van Poelgeest et al., “High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer,” Cancer Research, vol. 67, no. 1, pp. 354–361, 2007. View at Publisher · View at Google Scholar · View at PubMed
  9. K. I. Al-Shibli, T. Donnem, S. Al-Saad, M. Persson, R. M. Bremnes, and L.-T. Busund, “Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer,” Clinical Cancer Research, vol. 14, no. 16, pp. 5220–5227, 2008. View at Publisher · View at Google Scholar · View at PubMed
  10. D. G. DeNardo, M. Johansson, and L. M. Coussens, “Immune cells as mediators of solid tumor metastasis,” Cancer and Metastasis Reviews, vol. 27, no. 1, pp. 11–18, 2008. View at Publisher · View at Google Scholar · View at PubMed
  11. T. Yamaguchi and S. Sakaguchi, “Regulatory T cells in immune surveillance and treatment of cancer,” Seminars in Cancer Biology, vol. 16, no. 2, pp. 115–123, 2006. View at Publisher · View at Google Scholar · View at PubMed
  12. 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 PubMed
  13. A. Mantovani, S. Sozzani, M. Locati, P. Allavena, and A. Sica, “Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes,” Trends in Immunology, vol. 23, no. 11, pp. 549–555, 2002. View at Publisher · View at Google Scholar
  14. Y. Luo, H. Zhou, J. Krueger et al., “Targeting tumor-associated macrophages as a novel strategy against breast cancer,” Journal of Clinical Investigation, vol. 116, no. 8, pp. 2132–2141, 2006. View at Publisher · View at Google Scholar · View at PubMed
  15. D. G. DeNardo, J. B. Barreto, P. Andreu et al., “CD4+ T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages,” Cancer Cell, vol. 16, no. 2, pp. 91–102, 2009. View at Publisher · View at Google Scholar · View at PubMed
  16. A. Ziegler, R. Heidenreich, H. Braumuller et al., “EpCAM, a human tumor-associated antigen promotes Th2 development and tumor immune evasion,” Blood, vol. 113, no. 15, pp. 3494–3502, 2009. View at Publisher · View at Google Scholar · View at PubMed
  17. F. M. Marincola, E. M. Jaffee, D. J. Hickljn, and S. Ferrone, “Escape of human solid tumors from t-cell recognition: molecular mechanisms and functional significance,” Advances in Immunology, no. 74, pp. 181–273, 2000. View at Google Scholar
  18. 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 PubMed
  19. G. L. Sica, I.-H. Choi, G. Zhu et al., “B7-H4, a molecule of the B7 family, negatively regulates T cell immunity,” Immunity, vol. 18, no. 6, pp. 849–861, 2003. View at Publisher · View at Google Scholar
  20. G. Driessens, J. Kline, and T. F. Gajewski, “Costimulatory and coinhibitory receptors in anti-tumor immunity,” Immunological Reviews, vol. 229, no. 1, pp. 126–144, 2009. View at Publisher · View at Google Scholar · View at PubMed
  21. D. A. Thomas and J. Massague, “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 PubMed
  22. M. Kurte, M. Lopez, A. Aguirre et al., “A synthetic peptide homologous to functional domain of human IL-10 down-regulates expression of MHC class I and transporter associated with antigen processing 1/2 in human melanoma cells,” Journal of Immunology, vol. 173, no. 3, pp. 1731–1737, 2004. View at Google Scholar
  23. M. Terabe, S. Matsui, N. Noben-Trauth et al., “NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway,” Nature Immunology, vol. 1, no. 6, pp. 515–520, 2000. View at Google Scholar
  24. D. I. Gabrilovich, H. L. Chen, K. R. Girgis et al., “Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells,” Nature Medicine, vol. 2, no. 10, pp. 1096–1103, 1996. View at Publisher · View at Google Scholar
  25. J. L. Marshall, R. J. Hoyer, M. A. Toomey et al., “Phase I study in advanced cancer patients of a diversified prime-and-boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses,” Journal of Clinical Oncology, vol. 18, no. 23, pp. 3964–3973, 2000. View at Google Scholar
  26. A. L. Boehm, J. Higgins, A. Franzusoff, J. Schlom, and J. W. Hodge, “Concurrent vaccination with two distinct vaccine platforms targeting the same antigen generates phenotypically and functionally distinct T-cell populations,” Cancer Immunology, Immunotherapy, vol. 59, no. 3, pp. 397–408, 2010. View at Publisher · View at Google Scholar · View at PubMed
  27. M. A. Cheever, J. P. Allison, A. S. Ferris et al., “The prioritization of cancer antigens: a National Cancer Institute pilot project for the acceleration of translational research,” Clinical Cancer Research, vol. 15, no. 17, pp. 5323–5337, 2009. View at Publisher · View at Google Scholar · View at PubMed
  28. P. van der Bruggen, V. Stroobant, A. van Pel, and B. van den Eynde, “T-cell defined tumor antigens,” http://www.cancerimmunity.org/peptidedatabase/Tcellepitopes.htm.
  29. S. I. Abrams, S. F. Stanziale, S. D. Lunin, S. Zaremba, and J. Schlom, “Identification of overlapping epitopes in mutant ras oncogene peptides that activate CD4+ and CD8+ T cell responses,” European Journal of Immunology, vol. 26, no. 2, pp. 435–443, 1996. View at Publisher · View at Google Scholar · View at PubMed
  30. R. Offringa, M. P. M. Vierboom, S. H. van der Burg, L. Erdile, and C. J. M. Melief, “p53: a potential target antigen for immunotherapy of cancer,” Annals of the New York Academy of Sciences, vol. 910, pp. 223–236, 2000. View at Google Scholar
  31. J. H. Kessler, S. A. Bres-Vloemans, P. A. van Veelen et al., “BCR-ABL fusion regions as a source of multiple leukemia-specific CD8+ T-cell epitopes,” Leukemia, vol. 20, no. 10, pp. 1738–1750, 2006. View at Publisher · View at Google Scholar · View at PubMed
  32. K. L. Knutson, H. Lu, B. Stone et al., “Immunoediting of cancers may lead to epithelial to mesenchymal transition,” Journal of Immunology, vol. 177, no. 3, pp. 1526–1533, 2006. View at Google Scholar
  33. M. Kmieciak, K. L. Knutson, C. I. Dumur, and M. H. Manjili, “HER-2/neu antigen loss and relapse of mammary carcinoma are actively induced by T cell-mediated anti-tumor immune responses,” European Journal of Immunology, vol. 37, no. 3, pp. 675–685, 2007. View at Publisher · View at Google Scholar · View at PubMed
  34. E. Jager, M. Ringhoffer, J. Karbach, M. Arand, F. Oesch, and A. Knuth, “Inverse relationship of melanocyte differentiation antigen expression in melanoma tissues and CD8+ cytotoxic-T-cell responses: evidence for immunoselection of antigen-loss variants in vivo,” International Journal of Cancer, vol. 66, no. 4, pp. 470–476, 1996. View at Google Scholar
  35. Y. Hirohashi, T. Torigoe, S. Inoda et al., “The functioning antigens: beyond just as the immunological targets,” Cancer Science, vol. 100, no. 5, pp. 798–806, 2009. View at Publisher · View at Google Scholar
  36. J. P. Thiery and J. P. Sleeman, “Complex networks orchestrate epithelial-mesenchymal transitions,” Nature Reviews Molecular Cell Biology, vol. 7, no. 2, pp. 131–142, 2006. View at Publisher · View at Google Scholar · View at PubMed
  37. J. P. Thiery, “Epithelial-mesenchymal transitions in tumour progression,” Nature Reviews Cancer, vol. 2, no. 6, pp. 442–454, 2002. View at Google Scholar
  38. J. Yang, S. A. Mani, J. L. Donaher et al., “Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis,” Cell, vol. 117, no. 7, pp. 927–939, 2004. View at Publisher · View at Google Scholar · View at PubMed
  39. W. K. Kwok, M.-T. Ling, T.-W. Lee et al., “Up-regulation of TWIST in prostate cancer and its implication as a therapeutic target,” Cancer Research, vol. 65, no. 12, pp. 5153–5162, 2005. View at Publisher · View at Google Scholar · View at PubMed
  40. R. Kalluri and R. A. Weinberg, “The basics of epithelial-mesenchymal transition,” Journal of Clinical Investigation, vol. 119, no. 6, pp. 1420–1428, 2009. View at Publisher · View at Google Scholar · View at PubMed
  41. C. Palena, D. E. Polev, K. Y. Tsang et al., “The human T-box mesodermal transcription factor Brachyury is a candidate target for T-cell - mediated cancer immunotherapy,” Clinical Cancer Research, vol. 13, no. 8, pp. 2471–2478, 2007. View at Publisher · View at Google Scholar · View at PubMed
  42. R. I. Fernando, M. Litzinger, P. Trono, D. H. Hamilton, J. Schlom, and C. Palena, “The T-box transcription factor Brachyury promotes epithelial-mesenchymal transition in human tumor cells,” Journal of Clinical Investigation, vol. 120, no. 2, pp. 533–544, 2010. View at Publisher · View at Google Scholar · View at PubMed
  43. C. Kudo-Saito, J. Schlom, and J. W. Hodge, “Induction of an antigen cascade by diversified subcutaneous/intratumoral vaccination is associated with antitumor responses,” Clinical Cancer Research, vol. 11, no. 6, pp. 2416–2426, 2005. View at Publisher · View at Google Scholar · View at PubMed
  44. L. H. Butterfield, A. Ribas, V. B. Dissette et al., “Determinant spreading associated with clinical response in dendritic cell-based immunotherapy for malignant melanoma,” Clinical Cancer Research, vol. 9, no. 3, pp. 998–1008, 2003. View at Google Scholar
  45. P. M. Arlen, J. L. Gulley, C. Parker et al., “A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer,” Clinical Cancer Research, vol. 12, no. 4, pp. 1260–1269, 2006. View at Publisher · View at Google Scholar · View at PubMed
  46. R. H. Schwartz, “A cell culture model for T lymphocyte clonal anergy,” Science, vol. 248, no. 4961, pp. 1349–1356, 1990. View at Google Scholar
  47. F. A. Harding, J. G. McArthur, J. A. Gross, D. H. Raulet, and J. P. Allison, “CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones,” Nature, vol. 356, no. 6370, pp. 607–609, 1992. View at Publisher · View at Google Scholar · View at PubMed
  48. X. Zang and J. P. Allison, “The B7 family and cancer therapy: costimulation and coinhibition,” Clinical Cancer Research, vol. 13, no. 18, part 1, pp. 5271–5279, 2007. View at Publisher · View at Google Scholar · View at PubMed
  49. J. W. Hodge, J. P. McLaughlin, S. I. Abrams, W. L. Shupert, J. Schlom, and J. A. Kantor, “Admixture of a recombinant vaccinia virus containing the gene for the costimulatory molecule B7 and a recombinant vaccinia virus containing a tumor-associated antigen gene results in enhanced specific T-Cell responses and antitumor immunity,” Cancer Research, vol. 55, no. 16, pp. 3598–3603, 1995. View at Google Scholar
  50. J. W. Hodge, H. Sabzevari, A. G. Yafal, L. Gritz, M. G. O. Lorenz, and J. Schlom, “A triad of costimulatory molecules synergize to amplify T-cell activation,” Cancer Research, vol. 59, no. 22, pp. 5800–5807, 1999. View at Google Scholar
  51. M. Zhu, H. Terasawa, J. Gulley et al., “Enhanced activation of human T cells via avipox vector-mediated hyperexpression of a triad of costimulatory molecules in human dendritic cells,” Cancer Research, vol. 61, no. 9, pp. 3725–3734, 2001. View at Google Scholar
  52. C. Palena, M. Zhu, J. Schlom, and K.-Y. Tsang, “Human B cells that hyperexpress a triad of costimulatory molecules via avipox-vector infection: an alternative source of efficient antigen-presenting cells,” Blood, vol. 104, no. 1, pp. 192–199, 2004. View at Publisher · View at Google Scholar · View at PubMed
  53. P. W. Kantoff, T. J. Schuetz, B. A. Blumenstein et al., “Overall survival (OS) analysis of a phase II randomized controlled trial (RCT) of a poxviral-based PSA targeted immunotherapy in metastatic castration-resistant prostate cancer (mCRPC),” Journal of Clinical Oncology, vol. 28, no. 7, pp. 1099–1105, 2010. View at Google Scholar
  54. J. L. Gulley, P. M. Arlen, R. A. Madan et al., “Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer,” Cancer Immunology, Immunotherapy, vol. 59, no. 5, pp. 663–674, 2010. View at Publisher · View at Google Scholar · View at PubMed
  55. E. Kass, D. L. Panicali, G. Mazzara, J. Seldom, and J. W. Greiner, “Granulocyte/macrophage-colony stimulating factor produced by recombinant avian poxviruses enriches the regional lymph nodes with antigen-presenting cells and acts as an immunoadjuvant,” Cancer Research, vol. 61, no. 1, pp. 206–214, 2001. View at Google Scholar
  56. E. Kass, J. Parker, J. Schlom, and J. W. Greiner, “Comparative studies of the effects of recombinant GM-CSF and GM-CSF administered via a poxvirus to enhance the concentration of antigen- presenting cells in regional lymph nodes,” Cytokine, vol. 12, no. 7, pp. 960–971, 2000. View at Publisher · View at Google Scholar · View at PubMed
  57. G. Dranoff, E. Jaffee, A. Lazenby et al., “Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 8, pp. 3539–3543, 1993. View at Google Scholar
  58. G. Dranoff, “GM-CSF-secreting melanoma vaccines,” Oncogene, vol. 22, no. 20, pp. 3188–3192, 2003. View at Publisher · View at Google Scholar · View at PubMed
  59. G. Parmiani, C. Castelli, L. Pilla, M. Santinami, M. P. Colombo, and L. Rivoltini, “Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients,” Annals of Oncology, vol. 18, no. 2, pp. 226–232, 2007. View at Publisher · View at Google Scholar · View at PubMed
  60. E. J. Small, P. F. Schellhammer, C. S. Higano et al., “Placebo-controlled phase III trial of immunologic therapy with Sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer,” Journal of Clinical Oncology, vol. 24, no. 19, pp. 3089–3094, 2006. View at Publisher · View at Google Scholar · View at PubMed
  61. P. Schellhammer, C. Higano, E. Berger et al., “A randomized, double-blind, placebo-controlled multi-center, phase III trial of sipuleucel-T in men with metastatic, androgen independent prostatic adenocarcinoma (AIPC),” in Proceedings of the American Urological Association Annual Meeting, Chicago, Ill, USA, April 2009.
  62. F. O. Smith, S. G. Downey, J. A. Klapper et al., “Treatment of metastatic melanoma using Interleukin-2 alone or in conjunction with vaccines,” Clinical Cancer Research, vol. 14, no. 17, pp. 5610–5618, 2008. View at Publisher · View at Google Scholar · View at PubMed
  63. B. Heemskerk, K. Liu, M. E. Dudley et al., “Adoptive cell therapy for patients with melanoma, using tumor-infiltrating lymphocytes genetically engineered to secrete interleukin-2,” Human Gene Therapy, vol. 19, no. 5, pp. 496–510, 2008. View at Publisher · View at Google Scholar · View at PubMed
  64. F. Melchionda, T. J. Fry, M. J. Milliron, M. A. McKirdy, Y. Tagaya, and C. L. Mackall, “Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8+ memory cell pool,” Journal of Clinical Investigation, vol. 115, no. 5, pp. 1177–1187, 2005. View at Publisher · View at Google Scholar
  65. T. A. Waldmann, “The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design,” Nature Reviews Immunology, vol. 6, no. 8, pp. 595–601, 2006. View at Publisher · View at Google Scholar · View at PubMed
  66. N. Sato, H. J. Patel, T. A. Waldmann, and Y. Tagaya, “The IL-15/IL-15Rα on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 2, pp. 588–593, 2007. View at Publisher · View at Google Scholar · View at PubMed
  67. M. A. Cheever, “Twelve immunotherapy drugs that could cure cancers,” Immunological Reviews, vol. 222, no. 1, pp. 357–368, 2008. View at Publisher · View at Google Scholar · View at PubMed
  68. D. F. McDermott and M. B. Atkins, “Immunotherapy of metastatic renal cell carcinoma,” Cancer Journal, vol. 14, no. 5, pp. 320–324, 2008. View at Google Scholar
  69. T. Petrella, I. Quirt, S. Verma, A. E. Haynes, M. Charette, and K. Bak, “Single-agent interleukin-2 in the treatment of metastatic melanoma: a systematic review,” Cancer Treatment Reviews, vol. 33, no. 5, pp. 484–496, 2007. View at Publisher · View at Google Scholar · View at PubMed
  70. M. Rosenstein, S. E. Ettinghausen, and S. A. Rosenberg, “Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2,” Journal of Immunology, vol. 137, no. 5, pp. 1735–1742, 1986. View at Google Scholar
  71. M. Ahmadzadeh and S. A. Rosenberg, “IL-2 administration increases CD4+CD25hi Foxp3+ regulatory T cells in cancer patients,” Blood, vol. 107, no. 6, pp. 2409–2414, 2006. View at Publisher · View at Google Scholar · View at PubMed
  72. M. E. Dudley, J. R. Wunderlich, T. E. Shelton, J. Even, and S. A. Rosenberg, “Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients,” Journal of Immunotherapy, vol. 26, no. 4, pp. 332–342, 2003. View at Publisher · View at Google Scholar
  73. F. Villinger, R. Miller, K. Mori et al., “IL-15 is superior to IL-2 in the generation of long-lived antigen specific memory CD4 and CD8 T cells in rhesus macaques,” Vaccine, vol. 22, no. 25-26, pp. 3510–3521, 2004. View at Publisher · View at Google Scholar · View at PubMed
  74. M. A. Kutzler, T. M. Robinson, M. A. Chattergoon et al., “Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help,” Journal of Immunology, vol. 175, no. 1, pp. 112–123, 2005. View at Google Scholar
  75. M. P. Colombo and G. Trinchieri, “Interleukin-12 in anti-tumor immunity and immunotherapy,” Cytokine and Growth Factor Reviews, vol. 13, no. 2, pp. 155–168, 2002. View at Publisher · View at Google Scholar
  76. J. P. Leonard, M. L. Sherman, G. L. Fisher et al., “Effects of single-dose interleukin-12 exposure on interleukin-12 associated toxicity and interferon-γ production,” Blood, vol. 90, no. 7, pp. 2541–2548, 1997. View at Google Scholar
  77. D. A. Zaharoff, B. S. Hoffman, H. B. Hooper et al., “Intravesical immunotherapy of superficial bladder cancer with chitosan/interleukin-12,” Cancer Research, vol. 69, no. 15, pp. 6192–6199, 2009. View at Publisher · View at Google Scholar · View at PubMed
  78. M. Chakraborty, S. I. Abrams, K. Camphausen et al., “Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy,” Journal of Immunology, vol. 170, no. 12, pp. 6338–6347, 2003. View at Google Scholar
  79. C. T. Garnett, C. Palena, M. Chakarborty, K.-Y. Tsang, J. Schlom, and J. W. Hodge, “Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes,” Cancer Research, vol. 64, no. 21, pp. 7985–7994, 2004. View at Publisher · View at Google Scholar · View at PubMed
  80. E. A. Reits, J. W. Hodge, C. A. Herberts et al., “Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy,” Journal of Experimental Medicine, vol. 203, no. 5, pp. 1259–1271, 2006. View at Publisher · View at Google Scholar · View at PubMed
  81. M. Chakraborty, S. I. Abrams, C. N. Coleman, K. Camphausen, J. Schlom, and J. W. Hodge, “External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing,” Cancer Research, vol. 64, no. 12, pp. 4328–4337, 2004. View at Publisher · View at Google Scholar · View at PubMed
  82. J. L. Gulley, P. M. Arlen, A. Bastian et al., “Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer,” Clinical Cancer Research, vol. 11, no. 9, pp. 3353–3362, 2005. View at Publisher · View at Google Scholar · View at PubMed
  83. R. A. Lake and R. G. van der Most, “A better way for a cancer cell to die,” The New England Journal of Medicine, vol. 354, no. 23, pp. 2503–2504, 2006. View at Publisher · View at Google Scholar · View at PubMed
  84. 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 PubMed
  85. E. S. Bergmann-Leitner and S. I. Abrams, “Treatment of human colon carcinoma cell lines with anti-neoplastic agents enhances their lytic sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes,” Cancer Immunology, Immunotherapy, vol. 50, no. 9, pp. 445–455, 2001. View at Publisher · View at Google Scholar
  86. X. X. Wu, Y. Zeng, X. H. Jin, and Y. Kakehi, “Enhanced susceptibility of adriamycin-treated human renal cell carcinoma cells to lysis by peripheral blood lymphocytes and tumor infiltrating lymphocytes,” Oncology Reports, vol. 18, no. 2, pp. 353–359, 2007. View at Google Scholar
  87. O. T. M. Chan and L.-X. Yang, “The immunological effects of taxanes,” Cancer Immunology, Immunotherapy, vol. 49, no. 4-5, pp. 181–185, 2000. View at Google Scholar
  88. C. T. Garnett, J. Schlom, and J. W. Hodge, “Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: effects of docetaxel on immune enhancement,” Clinical Cancer Research, vol. 14, no. 11, pp. 3536–3544, 2008. View at Publisher · View at Google Scholar · View at PubMed
  89. J.-P. H. Machiels, R. T. Reilly, L. A. Emens et al., “Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice,” Cancer Research, vol. 61, no. 9, pp. 3689–3697, 2001. View at Google Scholar
  90. C. Galustian, M.-C. Labarthe, J. B. Bartlett, and A. G. Dalgleish, “Thalidomide-derived immunomodulatory drugs as therapeutic agents,” Expert Opinion on Biological Therapy, vol. 4, no. 12, pp. 1963–1970, 2004. View at Publisher · View at Google Scholar · View at PubMed
  91. C. Galustian, B. Meyer, M.-C. Labarthe et al., “The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells,” Cancer Immunology, Immunotherapy, vol. 58, no. 7, pp. 1033–1045, 2009. View at Publisher · View at Google Scholar · View at PubMed
  92. B. Farsaci, H. Sabzevari, M. G. Di Bari, S. Takai, J. Schlom, and J. W. Hodge, “Effect of a small molecule BCL-2 inhibitor on immune function and use with a recombinant vaccine,” International Journal of Cancer, 2010 Jan 20. [Epub ahead of print].
  93. 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 PubMed
  94. F. Hirano, K. Kaneko, H. Tamura et al., “Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity,” Cancer Research, vol. 65, no. 3, pp. 1089–1096, 2005. View at Google Scholar
  95. D. V. R. Prasad, S. Richards, X. M. Mai, and C. Dong, “B7S1, a novel B7 family member that negatively regulates T cell activation,” Immunity, vol. 18, no. 6, pp. 863–873, 2003. View at Publisher · View at Google Scholar
  96. B. Tringler, S. Zhuo, G. Pilkington et al., “B7-H4 is highly expressed in ductal and lobular breast cancer,” Clinical Cancer Research, vol. 11, no. 5, pp. 1842–1848, 2005. View at Publisher · View at Google Scholar · View at PubMed
  97. B. Tringler, W. Liu, L. Corral et al., “B7-H4 overexpression in ovarian tumors,” Gynecologic Oncology, vol. 100, no. 1, pp. 44–52, 2006. View at Publisher · View at Google Scholar · View at PubMed
  98. Y. Sun, Y. Wang, J. Zhao et al., “B7-H3 and B7-H4 expression in non-small-cell lung cancer,” Lung Cancer, vol. 53, no. 2, pp. 143–151, 2006. View at Publisher · View at Google Scholar · View at PubMed
  99. A. E. Krambeck, R. H. Thompson, H. Dong et al., “B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 27, pp. 10391–10396, 2006. View at Publisher · View at Google Scholar · View at PubMed
  100. J. G. Egen and J. P. Allison, “Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength,” Immunity, vol. 16, no. 1, pp. 23–35, 2002. View at Publisher · View at Google Scholar
  101. J. G. Egen, M. S. Kuhns, and J. P. Allison, “CTLA-4: new insights into its biological function and use in tumor immunotherapy,” Nature Immunology, vol. 3, no. 7, pp. 611–618, 2002. View at Publisher · View at Google Scholar · View at PubMed
  102. J. W. Hodge, M. Chakraborty, C. Kudo-Saito, C. T. Garnett, and J. Schlom, “Multiple costimulatory modalities enhance CTL avidity,” Journal of Immunology, vol. 174, no. 10, pp. 5994–6004, 2005. View at Google Scholar
  103. 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 PubMed
  104. 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 PubMed
  105. 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 Google Scholar
  106. M. Gavin and A. Rudensky, “Control of immune homeostasis by naturally arising regulatory CD4+ T cells,” Current Opinion in Immunology, vol. 15, no. 6, pp. 690–696, 2003. View at Publisher · View at Google Scholar
  107. S. Sakaguchi, “Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self,” Nature Immunology, vol. 6, no. 4, pp. 345–352, 2005. View at Publisher · View at Google Scholar · View at PubMed
  108. E. Y. Woo, C. S. Chu, T. J. Goletz et al., “Regulatory CD4+CD25+ T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer,” Cancer Research, vol. 61, no. 12, pp. 4766–4772, 2001. View at Google Scholar
  109. 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 Google Scholar
  110. S. Onizuka, I. Tawara, J. Shimizu, S. Sakaguchi, T. Fujita, and E. Nakayama, “Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor α) monoclonal antibody,” Cancer Research, vol. 59, no. 13, pp. 3128–3133, 1999. View at Google Scholar
  111. J. Shimizu, S. Yamazaki, and S. Sakaguchi, “Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity,” Journal of Immunology, vol. 163, no. 10, pp. 5211–5218, 1999. View at Google Scholar
  112. C. Kudo-Saito, J. Schlom, K. Camphausen, C. N. Coleman, and J. W. Hodge, “The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors,” Clinical Cancer Research, vol. 11, no. 12, pp. 4533–4544, 2005. View at Publisher · View at Google Scholar · View at PubMed
  113. M. T. Litzinger, R. Fernando, T. J. Curiel, D. W. Grosenbach, J. Schlom, and C. Palena, “IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity,” Blood, vol. 110, no. 9, pp. 3192–3201, 2007. View at Publisher · View at Google Scholar · View at PubMed
  114. B. Barnett, I. Kryczek, P. Cheng, W. Zou, and T. J. Curiel, “Regulatory T cells in ovarian cancer: biology and therapeutic potential,” American Journal of Reproductive Immunology, vol. 54, no. 6, pp. 369–377, 2005. View at Publisher · View at Google Scholar · View at PubMed
  115. K. Mahnke, K. Schonfeld, S. Fondel et al., “Depletion of CD4+CD25+ human regulatory T cells in vivo: kinetics of Treg depletion and alterations in immune functions in vivo and in vitro,” International Journal of Cancer, vol. 120, no. 12, pp. 2723–2733, 2007. View at Publisher · View at Google Scholar · View at PubMed
  116. 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 PubMed
  117. J. Dannull, Z. Su, D. Rizzieri et al., “Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells,” Journal of Clinical Investigation, vol. 115, no. 12, pp. 3623–3633, 2005. View at Publisher · View at Google Scholar · View at PubMed
  118. G. C. Blobe, W. P. Schiemann, and H. F. Lodish, “Role of transforming growth factor β in human disease,” The New England Journal of Medicine, vol. 342, no. 18, pp. 1350–1358, 2000. View at Publisher · View at Google Scholar
  119. B. A. Teicher, “Malignant cells, directors of the malignant process: role of transforming growth factor-beta,” Cancer and Metastasis Reviews, vol. 20, no. 1-2, pp. 133–143, 2001. View at Publisher · View at Google Scholar
  120. S. H. Wrzesinski, Y. Y. Wan, and R. A. Flavell, “Transforming growth factor-β and the immune response: implications for anticancer therapy,” Clinical Cancer Research, vol. 13, no. 18, part 1, pp. 5262–5270, 2007. View at Publisher · View at Google Scholar · View at PubMed
  121. 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 PubMed
  122. M. Terabe, E. Ambrosino, S. Takaku et al., “Synergistic enhancement of CD8+ T cell-mediated tumor vaccine efficacy by an anti-transforming growth factor-β monoclonal antibody,” Clinical Cancer Research, vol. 15, no. 21, pp. 6560–6569, 2009. View at Publisher · View at Google Scholar · View at PubMed
  123. J. Folkman, “Angiogenesis in cancer, vascular, rheumatoid and other disease,” Nature Medicine, vol. 1, no. 1, pp. 27–31, 1995. View at Google Scholar
  124. K. J. Kim, B. Li, J. Winer et al., “Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo,” Nature, vol. 362, no. 6423, pp. 841–844, 1993. View at Publisher · View at Google Scholar · View at PubMed
  125. P. Allavena, A. Sica, C. Garlanda, and A. Mantovani, “The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance,” Immunological Reviews, vol. 222, no. 1, pp. 155–161, 2008. View at Publisher · View at Google Scholar · View at PubMed
  126. D. I. Gabrilovich, T. Ishida, S. Nadaf, J. E. Ohm, and D. P. Carbone, “Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function,” Clinical Cancer Research, vol. 5, no. 10, pp. 2963–2970, 1999. View at Google Scholar