Immunologic Aspects of Prostate Cancer

  • Christine Galustian
  • Oussama Elhage
  • Richard Smith
  • Prokar Dasgupta


The concept that cancer can be eliminated by the immune system has been put forward over 100 years ago [1]. At this time, it was already thought that immune effector cells can recognize cancer cells as non-self and can eliminate them in the same way as viral or microbial pathogens. Both the innate immune system and the adaptive immune system have a major role in the control of tumor cell growth. The innate immune system consists of nonantigen-specific cells including macrophages, dendritic cells, neutrophils, natural killer cells, gamma delta T cells, and complement. The adaptive immune system consists of cells such as antigen-specific cytotoxic and helper T cells and antibody-producing B cells which can obtain a memory phenotype against specific antigenic challenge. The result is the ability of the different immune cell types to recognize cancer cells as foreign [2]. Antigens produced by tumor cells are known to be recognized by T cells and B cells, and both tumor antigen-specific T cells and antibodies against tumor antigens can be detected in patients with cancers such as melanoma, ovarian cancer, colorectal carcinoma, and hepatocellular cell carcinoma [3, 4]. Tumor-related antigens fall into a number of types including unique patient or shared tumor-specific antigens, antigens which are in both tumors and normal tissues, and antigens derived from tumor-associated viruses. In prostate cancer, a number of antigens are expressed which can be used for prostate cancer diagnosis or monitoring (Table 5.1).


Prostate Cancer Prostate Cancer Patient Antitumor Immune Response Prostate Acid Phosphatase Fowlpox Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Ehrlich P. Collected studies in immunity. New York: Wiley; 1906.Google Scholar
  2. 2.
    Burnet M. Cancer; a biological approach. I. The processes of control. Br Med J. 1957;1:779–86.PubMedCrossRefGoogle Scholar
  3. 3.
    Zusman I, Ben-Hur H. Serological markers for detection of cancer (review). Int J Mol Med. 2001;7:547–56.PubMedGoogle Scholar
  4. 4.
    Zhang JY, Tan EM. Autoantibodies to tumor-associated antigens as diagnostic biomarkers in hepatocellular carcinoma and other solid tumors. Expert Rev Mol Diagn. 2010;10:321–8.PubMedCrossRefGoogle Scholar
  5. 5.
    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 U S A. 2008;105:3509–14.PubMedCrossRefGoogle Scholar
  6. 6.
    Suyama T, et al. Expression of cancer/testis antigens in prostate cancer is associated with disease progression. Prostate. 2010;70:1778–87.PubMedGoogle Scholar
  7. 7.
    Jaraj SJ, et al. GAD1 is a biomarker for benign and malignant prostatic tissue. Scand J Urol Nephrol. 2011;45:39–45. Epub 2010 Nov 22.PubMedCrossRefGoogle Scholar
  8. 8.
    Kim YR, et al. Differential CARM1 expression in prostate and colorectal cancers. BMC Cancer. 2010;10:197.PubMedCrossRefGoogle Scholar
  9. 9.
    Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3:81–5.PubMedGoogle Scholar
  10. 10.
    Lilja H, Ulmert D, Vickers AJ. Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat Rev Cancer. 2008;8:268–78.PubMedCrossRefGoogle Scholar
  11. 11.
    Hall CL, Daignault SD, Shah RB, Pienta KJ, Keller ET. Dickkopf-1 expression increases early in prostate cancer development and decreases during progression from primary tumor to metastasis. Prostate. 2008;68:1396–404.PubMedCrossRefGoogle Scholar
  12. 12.
    Whitaker NJ, Glenn WK, Sahrudin A et al. Human papillomavirus and Epstein Barr virus in prostate cancer: Koilocytes indicate potential oncogenic influences of human papillomavirus in prostate cancer. The Prostate 2012 in press.PubMedCrossRefGoogle Scholar
  13. 13.
    Smyth MJ, Hayakawa Y, Takeda K, Yagita H. New aspects of natural-killer-cell surveillance and therapy of cancer. Nat Rev Cancer. 2002;2:850–61.PubMedCrossRefGoogle Scholar
  14. 14.
    Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity. 2004;21:137–48.PubMedCrossRefGoogle Scholar
  15. 15.
    Rajarubendra N, Lawrentschuk N, Bolton DM, Klotz L, Davis ID. Prostate cancer immunology – an update for urologists. BJU Int. 2011;107:1046–51.PubMedCrossRefGoogle Scholar
  16. 16.
    Teng MWL, Swann JB, Koebel CM, Schreiber RD, Smyth MJ. Immune-mediated dormancy: an equilibrium with cancer. J Leukoc Biol. 2008;84:988–93.PubMedCrossRefGoogle Scholar
  17. 17.
    Hussein MR, Al-Assiri M, Musalam AO. Phenotypic characterization of the infiltrating immune cells in normal prostate, benign nodular prostatic hyperplasia and prostatic adenocarcinoma. Exp Mol Pathol. 2009;86:108–13.PubMedCrossRefGoogle Scholar
  18. 18.
    Kiniwa Y, et al. CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer. Clin Cancer Res. 2007;13:6947–58.PubMedCrossRefGoogle Scholar
  19. 19.
    Shafer-Weaver KA, et al. Cutting edge: tumor-specific CD8+ T cells infiltrating prostatic tumors are induced to become suppressor cells. J Immunol. 2009;183:4848–52.PubMedCrossRefGoogle Scholar
  20. 20.
    Kraman M, et al. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science. 2010;330:827–30.PubMedCrossRefGoogle Scholar
  21. 21.
    McAlhany SJ, et al. Decreased stromal expression and increased epithelial expression of WFDC1/ps20 in prostate cancer is associated with reduced recurrence-free survival. Prostate. 2004;61:182–91.PubMedCrossRefGoogle Scholar
  22. 22.
    Zhao WP, Zhu B, Duan YZ, Chen ZT. Neutralization of complement regulatory proteins CD55 and CD59 augments therapeutic effect of herceptin against lung carcinoma cells. Oncol Rep. 2009;21:1405–11.PubMedGoogle Scholar
  23. 23.
    Geis N, et al. Inhibition of membrane complement inhibitor expression (CD46, CD55, CD59) by siRNA sensitizes tumor cells to complement attack in vitro. Curr Cancer Drug Targets. 2010;10:922–31.PubMedCrossRefGoogle Scholar
  24. 24.
    Han SL, et al. The impact of expressions of CD97 and its ligand CD55 at the invasion front on prognosis of rectal adenocarcinoma. Int J Colorectal Dis. 2010;25:695–702.PubMedCrossRefGoogle Scholar
  25. 25.
    Loberg RD, Wojno KJ, Day LL, Pienta KJ. Analysis of membrane-bound complement regulatory proteins in prostate cancer. Urology. 2005;66:1321–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Blades RA, Keating PJ, McWilliam LJ, George NJ, Stern PL. Loss of HLA class I expression in prostate cancer: implications for immunotherapy. Urology. 1995;46:681–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Lu QL, Abel P, Mitchell S, Foster C, Lalani EN. Decreased HLA-A expression in prostate cancer is associated with normal allele dosage in the majority of cases. J Pathol. 2000;190:169–76.PubMedCrossRefGoogle Scholar
  28. 28.
    Ciavarra RP, et al. Flt3-ligand induces transient tumor regression in an ectopic treatment model of major histocompatibility complex-negative prostate cancer. Cancer Res. 2000;60:2081–4.PubMedGoogle Scholar
  29. 29.
    Garnett CT, et al. Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes. Cancer Res. 2004;64:7985–94.PubMedCrossRefGoogle Scholar
  30. 30.
    Reinis M. Immunotherapy of MHC class I-deficient tumors. Future Oncol. 2010;6:1577–89.PubMedCrossRefGoogle Scholar
  31. 31.
    Karre K. NK cells, MHC class I molecules and the missing self. Scand J Immunol. 2002;55:221–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Uhrberg M, et al. Human diversity in killer cell inhibitory receptor genes. Immunity. 1997;7:753–63.PubMedCrossRefGoogle Scholar
  33. 33.
    Barten R, Torkar M, Haude A, Trowsdale J, Wilson MJ. Divergent and convergent evolution of NK-cell receptors. Trends Immunol. 2001;22:52–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol. 2002;20:217–51.PubMedCrossRefGoogle Scholar
  35. 35.
    Brown D, Trowsdale J, Allen R. The LILR family: modulators of innate and adaptive immune pathways in health and disease. Tissue Antigens. 2004;64:215–25.PubMedCrossRefGoogle Scholar
  36. 36.
    Brown DP, et al. The inhibitory receptor LILRB4 (ILT3) modulates antigen presenting cell phenotype and, along with LILRB2 (ILT4), is upregulated in response to Salmonella infection. BMC Immunol. 2009;10:56.PubMedCrossRefGoogle Scholar
  37. 37.
    McIntire RH, et al. Novel HLA-G-binding leukocyte ­immunoglobulin-like receptor (LILR) expression patterns in human placentas and umbilical cords. Placenta. 2008;29:631–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Young NT, et al. The inhibitory receptor LILRB1 modulates the differentiation and regulatory potential of human dendritic cells. Blood. 2008;111:3090–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Amiot L, et al. HLA-G transcription studies during the different stages of normal and malignant hematopoiesis. Tissue Antigens. 1996;48:609–14.PubMedCrossRefGoogle Scholar
  40. 40.
    Kuroki K, Maenaka K. Immune modulation of HLA-G dimer in maternal-fetal interface. Eur J Immunol. 2007;37:1727–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Seliger B, Abken H, Ferrone S. HLA-G and MIC expression in tumors and their role in anti-tumor immunity. Trends Immunol. 2003;24:82–7.PubMedCrossRefGoogle Scholar
  42. 42.
    Braud VM, McMichael AJ. Regulation of NK cell functions through interaction of the CD94/NKG2 receptors with the nonclassical class I molecule HLA-E. Curr Top Microbiol Immunol. 1999;244:85–95.PubMedCrossRefGoogle Scholar
  43. 43.
    Dranoff G, 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. Proc Natl Acad Sci U S A. 1993;90:3539–43.PubMedCrossRefGoogle Scholar
  44. 44.
    Simons JW, et al. Phase I/II trial of an allogeneic cellular immunotherapy in hormone-naïve prostate cancer. Clin Cancer Res. 2006;12:3394–401.PubMedCrossRefGoogle Scholar
  45. 45.
    Hodge JW, et al. A triad of costimulatory molecules synergize to amplify T-cell activation. Cancer Res. 1999;59:5800–7.PubMedGoogle Scholar
  46. 46.
    Johnson LE, et al. Safety and immunological efficacy of a prostate cancer plasmid DNA vaccine encoding prostatic acid phosphatase (PAP). Vaccine. 2006;24:293–303.PubMedCrossRefGoogle Scholar
  47. 47.
    Johnson LE, Frye TP, Chinnasamy N, Chinnasamy D, McNeel DG. Plasmid DNA vaccine encoding prostatic acid phosphatase is effective in eliciting autologous antigen-specific CD8+ T cells. Cancer Immunol Immunother. 2007;56:885–95.PubMedCrossRefGoogle Scholar
  48. 48.
    Small EJ, et al. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol. 2000;18:3894–903.PubMedGoogle Scholar
  49. 49.
    Bander NH, et al. Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. J Clin Oncol. 2005;23:4591–601.PubMedCrossRefGoogle Scholar
  50. 50.
    Milowsky MI, et al. Phase I trial of yttrium-90-labeled anti-­prostate-specific membrane antigen monoclonal antibody J591 for androgen-independent prostate cancer. J Clin Oncol. 2004;22:2522–31.PubMedCrossRefGoogle Scholar
  51. 51.
    Waterhouse P, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995;270:985–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Read S, Malmström V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med. 2000;192:295–302.PubMedCrossRefGoogle Scholar
  53. 53.
    Krummel MF, Allison JP. CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J Exp Med. 1996;183:2533–40.PubMedCrossRefGoogle Scholar
  54. 54.
    Higano CS, et al. Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer. Cancer. 2008;113:975–84.PubMedCrossRefGoogle Scholar
  55. 55.
    Morse MD, McNeel DG. Prostate cancer patients on androgen deprivation therapy develop persistent changes in adaptive immune responses. Hum Immunol. 2010;71:496–504.PubMedCrossRefGoogle Scholar
  56. 56.
    Hurwitz MD, et al. Radiation therapy induces circulating serum Hsp72 in patients with prostate cancer. Radiother Oncol. 2010;95:350–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Apetoh L, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007;13:1050–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Higano C, et al. A phase III trial of GVAX immunotherapy for prostate cancer versus docetaxel plus prednisone in asymptomatic, castration-resistant prostate cancer (CRPC). Genitourinary Cancers Symposium (Florida). 2009.Google Scholar
  59. 59.
    Small EJ, et al. A phase III trial of GVAX immunotherapy for prostate cancer in combination with docetaxel versus docetaxel plus prednisone in symptomatic, castration-resistant prostate cancer (CRPC). Genitourinary Cancer Symposium (Florida). 2009.Google Scholar
  60. 60.
    Eder JP, et al. A phase I trial of a recombinant vaccinia virus expressing prostate-specific antigen in advanced prostate cancer. Clin Cancer Res. 2000;6:1632–8.PubMedGoogle Scholar
  61. 61.
    Kaufman HL, et al. Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2004;22:2122–32.PubMedCrossRefGoogle Scholar
  62. 62.
    Arlen PM, et al. Antiandrogen, vaccine and combination therapy in patients with nonmetastatic hormone refractory prostate cancer. J Urol. 2005;174:539–46.PubMedCrossRefGoogle Scholar
  63. 63.
    Kantoff PW, 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. 2010;28:1099–105.PubMedCrossRefGoogle Scholar
  64. 64.
    McNeel DG, et al. Safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer. J Clin Oncol. 2009;27:4047–54.PubMedCrossRefGoogle Scholar
  65. 65.
    Small EJ, et al. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006;24:3089–94.PubMedCrossRefGoogle Scholar
  66. 66.
    Kantoff PW, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  • Christine Galustian
    • 1
  • Oussama Elhage
    • 2
  • Richard Smith
    • 2
  • Prokar Dasgupta
    • 2
  1. 1.MRC Centre for Transplantation, Kings College LondonLondonUK
  2. 2.Division of Transplantation and Mucosal ImmunologyMRC centre for Transplantation and Urology Centre, Kings College London, Guys HospitalLondonUK

Personalised recommendations