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Unmasking the immune recognition of prostate cancer with CTLA4 blockade

Abstract

Although cancer cells can be immunogenic, tumour progression is associated with the evasion of immunosurveillance, the promotion of tumour tolerance and even the production of pro-tumorigenic factors by immune cells. Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) represents a crucial immune checkpoint, the blockade of which can potentiate anti-tumour immunity. CTLA4-blocking antibodies are now an established therapeutic approach for malignant melanoma, and clinical trials with CTLA4-specific antibodies in prostate cancer have also shown clinical activity. This treatment may provide insights into the targets that the immune system recognizes to drive tumour regression, and could potentially improve both outcome and toxicity for patients with prostate cancer.

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Figure 1: Immunotherapy for prostate cancer.
Figure 2: CTLA4-specific antibodies potentiate TH cell-dependent B cell activation.

References

  1. American Cancer Society. Cancer Facts & Figures. American Cancer Society [online], http://www.cancer.org/Research/CancerFactsFigures/index (2011).

  2. Howlader, N. et al. SEER Cancer Statistics Review 1975–2008 National Cancer Institute [online], http://seer.cancer.gov/csr/1975_2008/ (2011).

    Google Scholar 

  3. Knudsen, K. E. & Scher, H. I. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin. Cancer Res. 15, 4792–4798 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Laufer, M., Denmeade, S. R., Sinibaldi, V. J., Carducci, M. A. & Eisenberger, M. A. Complete androgen blockade for prostate cancer: what went wrong? J. Urol. 164, 3–9 (2000).

    CAS  PubMed  Google Scholar 

  5. Cha, E. & Fong, L. Immunotherapy for prostate cancer: biology and therapeutic approaches. J. Clin. Oncol. 29, 3677–3685 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Madan, R. A., Arlen, P. M., Mohebtash, M., Hodge, J. W. & Gulley, J. L. Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer. Expert Opin. Investig Drugs 18, 1001–1011 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Gupta, S., Carballido, E. & Fishman, M. Sipuleucel-T for therapy of asymptomatic or minimally symptomatic, castrate-refractory prostate cancer: an update and perspective among other treatments. Onco. Targets Ther. 4, 79–96 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Akhtar, N. H., Pail, O., Saran, A., Tyrell, L. & Tagawa, S. T. Prostate-specific membrane antigen-based therapeutics. Adv. Urol. 2012, 973820 (2012).

    PubMed  Google Scholar 

  9. Antonarakis, E. S. & Drake, C. G. Current status of immunological therapies for prostate cancer. Curr. Opin. Urol. 20, 241–246 (2010).

    PubMed  PubMed Central  Google Scholar 

  10. Clive, K. S. et al. Use of GM-CSF as an adjuvant with cancer vaccines: beneficial or detrimental? Expert Rev. Vaccines 9, 519–525 (2010).

    CAS  PubMed  Google Scholar 

  11. Brahmer, J. R. 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. J. Clin. Oncol. 28, 3167–3175 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Schaer, D. A., Cohen, A. D. & Wolchok, J. D. Anti-GITR antibodies--potential clinical applications for tumor immunotherapy. Curr. Opin. Investig Drugs 11, 1378–1386 (2010).

    CAS  PubMed  Google Scholar 

  13. Gerritsen, W. et al. A dose-escalation trial of GM-CSF-gene transduced allogeneic prostate cancer cellular immunotherapy in combination with a fully human anti-CTLA antibody (MDX-010, ipilimumab) in patients with metastatic hormone-refractory prostate cancer (mHRPC). J. Clin. Oncol. Abstr. 24 2500 (2006).

    Google Scholar 

  14. Ledford, H. Melanoma drug wins US approval. Nature 471, 561 (2011).

    CAS  PubMed  Google Scholar 

  15. Brunet, J. F. et al. A new member of the immunoglobulin superfamily — CTLA-4. Nature 328, 267–270 (1987).

    CAS  PubMed  Google Scholar 

  16. Peach, R. J. et al. Complementarity determining region 1 (CDR1)- and CDR3-analogous regions in CTLA-4 and CD28 determine the binding to B7–1 J. Exp. Med. 180, 2049–2058 (1994).

    CAS  Google Scholar 

  17. Stein, P. H., Fraser, J. D. & Weiss, A. The cytoplasmic domain of CD28 is both necessary and sufficient for costimulation of interleukin-2 secretion and association with phosphatidylinositol 3'-kinase. Mol. Cell Biol. 14, 3392–3402 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Chuang, E. et al. The CD28 and CTLA-4 receptors associate with the serine/threonine phosphatase PP2A. Immunity 13, 313–322 (2000).

    CAS  PubMed  Google Scholar 

  19. Dariavach, P., Mattei, M. G., Golstein, P. & Lefranc, M. P. Human Ig superfamily CTLA-4 gene: chromosomal localization and identity of protein sequence between murine and human CTLA-4 cytoplasmic domains. Eur. J. Immunol. 18, 1901–1905 (1988).

    CAS  PubMed  Google Scholar 

  20. Schwartz, R. H. Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 71, 1065–1068 (1992).

    CAS  PubMed  Google Scholar 

  21. Linsley, P. S. et al. Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J. Exp. Med. 173, 721–730 (1991).

    CAS  PubMed  Google Scholar 

  22. Linsley, P. S. et al. Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J. Exp. Med. 176, 1595–1604 (1992).

    CAS  PubMed  Google Scholar 

  23. Linsley, P. S. et al. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity 4, 535–543 (1996).

    CAS  PubMed  Google Scholar 

  24. Chuang, E. et al. Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression. J. Immunol. 159, 144–151 (1997).

    CAS  PubMed  Google Scholar 

  25. van der Merwe, P. A., Bodian, D. L., Daenke, S., Linsley, P. & Davis, S. J. CD80 (B7–1) binds both CD28 and CTLA-4 with a low affinity and very fast kinetics. J. Exp. Med. 185, 393–403 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Waterhouse, P. et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270, 985–988 (1995).

    CAS  PubMed  Google Scholar 

  27. Krummel, M. F. & Allison, J. P. CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J. Exp. Med. 183, 2533–2540 (1996).

    CAS  PubMed  Google Scholar 

  28. Masteller, E. L., Chuang, E., Mullen, A. C., Reiner, S. L. & Thompson, C. B. Structural analysis of CTLA-4 function in vivo. J. Immunol. 164, 5319–5327 (2000).

    CAS  PubMed  Google Scholar 

  29. Martin, M., Schneider, H., Azouz, A. & Rudd, C. E. Cytotoxic T lymphocyte antigen 4 and CD28 modulate cell surface raft expression in their regulation of T cell function. J. Exp. Med. 194, 1675–1681 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Schneider, H. et al. Reversal of the TCR stop signal by CTLA-4. Science 313, 1972–1975 (2006).

    CAS  PubMed  Google Scholar 

  31. Wing, K., Yamaguchi, T. & Sakaguchi, S. Cell-autonomous and -non-autonomous roles of CTLA-4 in immune regulation. Trends Immunol. 32, 428–433 (2011).

    CAS  PubMed  Google Scholar 

  32. Wing, K. & Sakaguchi, S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nature Immunol. 11, 7–13 (2010).

    CAS  Google Scholar 

  33. Takahashi, T. et al. Immunologic self-tolerance maintained by CD25+CD4+ regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 192, 303–310 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Read, S. et al. Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo. J. Immunol. 177, 4376–4383 (2006).

    CAS  PubMed  Google Scholar 

  35. Jain, N., Nguyen, H., Chambers, C. & Kang, J. Dual function of CTLA-4 in regulatory T cells and conventional T cells to prevent multiorgan autoimmunity. Proc. Natl Acad. Sci. USA 107, 1524–1528 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Peggs, K. S., Quezada, S. A., Chambers, C. A., Korman, A. J. & Allison, J. P. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J. Exp. Med. 206, 1717–1725 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Krummel, M. F. & Allison, J. P. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J. Exp. Med. 182, 459–465 (1995).

    CAS  PubMed  Google Scholar 

  38. Kearney, E. R. et al. Antigen-dependent clonal expansion of a trace population of antigen-specific CD4+ T cells in vivo is dependent on CD28 costimulation and inhibited by CTLA-4. J. Immunol. 155, 1032–1036 (1995).

    CAS  PubMed  Google Scholar 

  39. Leach, D. R., Krummel, M. F. & Allison, J. P. Enhancement of antitumor immunity by CTLA-4 blockade. Science 271, 1734–1736 (1996).

    Article  CAS  PubMed  Google Scholar 

  40. Foster, B. A., Gingrich, J. R., Kwon, E. D., Madias, C. & Greenberg, N. M. Characterization of prostatic epithelial cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Cancer Res. 57, 3325–3330 (1997).

    CAS  PubMed  Google Scholar 

  41. Kwon, E. D. et al. Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc. Natl Acad. Sci. USA 94, 8099–8103 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Kwon, E. D. et al. Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade immunotherapy. Proc. Natl Acad. Sci. USA 96, 15074–15079 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Hurwitz, A. A. et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res. 60, 2444–2448 (2000).

    CAS  PubMed  Google Scholar 

  44. Hurwitz, A. A., Yu, T. F., Leach, D. R. & Allison, J. P. CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc. Natl Acad. Sci. USA 95, 10067–10071 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Mokyr, M. B., Kalinichenko, T., Gorelik, L. & Bluestone, J. A. Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice. Cancer Res. 58, 5301–5304 (1998).

    CAS  PubMed  Google Scholar 

  46. Demaria, S. et al. Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin. Cancer Res. 11, 728–734 (2005).

    CAS  PubMed  Google Scholar 

  47. Matsumura, S. et al. Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells. J. Immunol. 181, 3099–3107 (2008).

    CAS  PubMed  Google Scholar 

  48. Ma, Y. et al. Chemotherapy and radiotherapy: cryptic anticancer vaccines. Semin. Immunol. 22, 113–124 (2010).

    PubMed  Google Scholar 

  49. Drake, C. G. et al. Androgen ablation mitigates tolerance to a prostate/prostate cancer-restricted antigen. Cancer Cell 7, 239–249 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Sutherland, J. S. et al. Activation of thymic regeneration in mice and humans following androgen blockade. J. Immunol. 175, 2741–2753 (2005).

    CAS  PubMed  Google Scholar 

  51. Perrin, P. J., Maldonado, J. H., Davis, T. A., June, C. H. & Racke, M. K. CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis. J. Immunol. 157, 1333–1336 (1996).

    CAS  PubMed  Google Scholar 

  52. Luhder, F., Hoglund, P., Allison, J. P., Benoist, C. & Mathis, D. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulates the unfolding of autoimmune diabetes. J. Exp. Med. 187, 427–432 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. van Elsas, A., Hurwitz, A. A. & Allison, J. P. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J. Exp. Med. 190, 355–366 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Keler, T. et al. Activity and safety of CTLA-4 blockade combined with vaccines in cynomolgus macaques. J. Immunol. 171, 6251–6259 (2003).

    CAS  PubMed  Google Scholar 

  55. Small, E. J. et al. A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer. Clin. Cancer Res. 13, 1810–1815 (2007).

    CAS  PubMed  Google Scholar 

  56. Fong, L. et al. Potentiating endogenous antitumor immunity to prostate cancer through combination immunotherapy with CTLA4 blockade and GM-CSF. Cancer Res. 69, 609–615 (2009).

    CAS  PubMed  Google Scholar 

  57. Harzstark, A. L. et al. Final results of a phase I study of CTLA-4 blockade in combination with GM-CSF for metastatic castration resistant prostate cancer (mCRPC). J. Clin. Oncol. Abstr. 28, 4689 (2010).

    Google Scholar 

  58. Gerritsen, W. et al. Expanded phase I combination trial of GVAX immunotherapy for prostate cancer and ipilimumab in patients with metastatic hormone-refractory prostate cancer (mHPRC). J. Clin. Oncol. Abstr. 26, 5146 (2008).

    Google Scholar 

  59. Santegoets, S. et al. Lymphoid and myeloid biomarkers for clinical outcome of ipilimumab and prostate GVAX treatment: tumor-related CTLA-4 expression by CD4+ T cells as a dominant predictor of survival. J. Immunother. Abstr. 34, 9 (2011).

    Google Scholar 

  60. Kantoff, P. W. et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J. Clin. Oncol. 28, 1099–1105 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Mohebtash, M. et al. Phase I trial of targeted therapy with PSA-TRICOM vaccine (V) and ipilimumab (ipi) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). J. Clin. Oncol. Abstr. 27, 5144 (2009).

    Google Scholar 

  62. Beer, T. M. et al. Phase I trial of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration resistant prostate cancer (mCRPC). J. Clin. Oncol. Abstr. 26, 5004 (2008).

    Google Scholar 

  63. Slovin, S. F. et al. Initial phase II experience of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration-resistant prostate cancer (mCRPC). J. Clin. Oncol. Abstr. 27, 5138 (2009).

    Google Scholar 

  64. Small, E. J. et al. Randomized phase II study comparing 4 monthly doses of ipilimumab (MDX-010) as a single agent or in combination with a single dose of docetaxel in patients with hormone-refractory prostate cancer. J. Clin. Oncol. Abstr. 24, 4609 (2006).

    Google Scholar 

  65. Tollefson, M. K. et al. A randomized phase II study of ipilimumab with androgen ablation compared with androgen ablation alone in patients with advanced prostate cancer. 2010 Genitourinary Cancers Symp. Abstr. 168 (2010).

  66. Lang, J. M., Staab, M. J., Liu, G., Wilding, G. & McNeel, D. G. Phase I dose-escalation trial of tremelimumab in combination with bicalutamide in patients with recurrent prostate cancer. J. Clin. Oncol. Abstr. 29, 174 (2011).

    Google Scholar 

  67. Robert, C. et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 364, 2517–2526 (2011).

    CAS  PubMed  Google Scholar 

  68. Wolchok, J. D. et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol. 11, 155–164 (2010).

    CAS  PubMed  Google Scholar 

  69. Madan, R. A. et al. Overall survival (OS) analysis of a phase I trial of a vector-based vaccine (PSA-TRICOM) and ipilimumab (Ipi) in the treatment of metastatic castration-resistant prostate cancer (mCRPC). J. Clin. Oncol. Abstr. 28, 2550 (2010).

    Google Scholar 

  70. Hodi, F. S. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711–723 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Comin-Anduix, B. et al. Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma. J. Transl. Med. 6, 22 (2008).

    PubMed  PubMed Central  Google Scholar 

  72. Liakou, C. I. et al. CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc. Natl Acad. Sci. USA 105, 14987–14992 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Phan, G. Q. et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Natl Acad. Sci. USA 100, 8372–8377 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Kavanagh, B. et al. CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion. Blood 112, 1175–1183 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Quezada, S. A., Peggs, K. S., Curran, M. A. & Allison, J. P. CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J. Clin. Invest. 116, 1935–1945 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Mitsui, J. et al. Two distinct mechanisms of augmented antitumor activity by modulation of immunostimulatory/inhibitory signals. Clin. Cancer Res. 16, 2781–2791 (2010).

    CAS  PubMed  Google Scholar 

  77. Fasso, M. et al. SPAS-1 (stimulator of prostatic adenocarcinoma-specific T cells)/SH3GLB2: A prostate tumor antigen identified by CTLA-4 blockade. Proc. Natl Acad. Sci. USA 105, 3509–3514 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Lapointe, J. et al. Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc. Natl Acad. Sci. USA 101, 811–816 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Yuan, J. et al. CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit. Proc. Natl Acad. Sci. USA 105, 20410–20415 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Dubovsky, J. A., Albertini, M. R. & McNeel, D. G. MAD-CT-2 identified as a novel melanoma cancer-testis antigen using phage immunoblot analysis. J. Immunother. 30, 675–683 (2007).

    CAS  PubMed  Google Scholar 

  81. Goff, S. L., Robbins, P. F., El-Gamil, M. & Rosenberg, S. A. No correlation between clinical response to CTLA-4 blockade and presence of NY-ESO-1 antibody in patients with metastatic melanoma. J. Immunother. 32, 884–885 (2009).

    PubMed  PubMed Central  Google Scholar 

  82. Yuan, J. et al. Integrated NY-ESO-1 antibody and CD8+ T-cell responses correlate with clinical benefit in advanced melanoma patients treated with ipilimumab. Proc. Natl Acad. Sci. USA 108, 16723–16728 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Jinushi, M., Hodi, F. S. & Dranoff, G. Therapy-induced antibodies to MHC class I chain-related protein A antagonize immune suppression and stimulate antitumor cytotoxicity. Proc. Natl Acad. Sci. USA 103, 9190–9195 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Schoenfeld, J. et al. Active immunotherapy induces antibody responses that target tumor angiogenesis. Cancer Res. 70, 10150–10160 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Chesney, J. et al. An essential role for macrophage migration inhibitory factor (MIF) in angiogenesis and the growth of a murine lymphoma. Mol. Med. 5, 181–191 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Fong, L. et al. Identification of novel prostate cancer-associated antigens through antibody profiling of prostate cancer patients treated with CTLA-4 blockade. J. Clin. Oncol. Abstr. 28, 2578 (2010).

    Google Scholar 

  87. Nesslinger, N. J. et al. Standard treatments induce antigen-specific immune responses in prostate cancer. Clin. Cancer Res. 13, 1493–1502 (2007).

    CAS  PubMed  Google Scholar 

  88. Morse, M. D. & McNeel, D. G. Prostate cancer patients on androgen deprivation therapy develop persistent changes in adaptive immune responses. Hum. Immunol. 71, 496–504 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

S.S.K. is supported by a Peter Michael Foundation Pelican Fellowship. E.C. is supported by an ASCO Young Investivator Award. L.F. is supported by NIH R01 CA136753 and the Prostate Cancer Foundation.

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Kwek, S., Cha, E. & Fong, L. Unmasking the immune recognition of prostate cancer with CTLA4 blockade. Nat Rev Cancer 12, 289–297 (2012). https://doi.org/10.1038/nrc3223

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