Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Prostate cancer: genes, environment, immunity and the use of immunotherapy

Prostate Cancer and Prostatic Diseases volume 11, pages 230–236 (2008)Cite this article

Abstract

Prostate cancer remains the most prevalent noncutaneous cancer, leading to almost 30 000 deaths every year in men in the United States. A large body of knowledge emphasizes a strong influence of epidemiological factors such as lifestyle, environment and diet, on the development of prostate cancer. Although risk reduction of prostate cancer has been somewhat successful, effective prevention is still lacking. Immunotherapeutic approaches, although moderately complicated, remain promising in an effort to control the progression and development of the disease. Taken together, the parameters of epidemiological studies and immunotherapeutic regimens might eventually be the most effective and preventive approach for prostate cancer. This review highlights some of the events associated with the development and prevention of prostate cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ . Cancer statistics, 2007. CA Cancer J Clin 2007; 57: 43–66.

    Article  PubMed  Google Scholar 

  2. McCracken M, Olsen M, Chen Jr MS, Jemal A, Thun M, Cokkinides V et al. Cancer incidence, mortality, and associated risk factors among Asian Americans of Chinese, Filipino, Vietnamese, Korean, and Japanese ethnicities. CA Cancer J Clin 2007; 57: 190–205.

    Article  PubMed  Google Scholar 

  3. Ozanne SE, Constancia M . Mechanisms of disease: the developmental origins of disease and the role of the epigenotype. Nat Clin Pract Endocrinol Metab 2007; 3: 539–546.

    Article  CAS  PubMed  Google Scholar 

  4. Travis LB . The epidemiology of second primary cancers. Cancer Epidemiol Biomarkers Prev 2006; 15: 2020–2026.

    Article  PubMed  Google Scholar 

  5. Botti C, Seregni E, Ferrari L, Martinetti A, Bombardieri E . Immunosuppressive factors: role in cancer development and progression. Int J Biol Markers 1998; 13: 51–69.

    Article  CAS  PubMed  Google Scholar 

  6. Mocellin S, Marincola FM, Young HA . Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol 2005; 78: 1043–1051.

    Article  CAS  PubMed  Google Scholar 

  7. Wolk A . Diet, lifestyle and risk of prostate cancer. Acta Oncol 2005; 44: 277–281.

    Article  PubMed  Google Scholar 

  8. Sonn GA, Aronson W, Litwin MS . Impact of diet on prostate cancer: a review. Prostate Cancer Prostatic Dis 2005; 8: 304–310.

    Article  CAS  PubMed  Google Scholar 

  9. Colditz GA, Sellers TA, Trapido E . Epidemiology—identifying the causes and preventability of cancer? Nat Rev Cancer 2006; 6: 75–83.

    Article  CAS  PubMed  Google Scholar 

  10. Monson RR, Christiani DC . Summary of the evidence: Occupation and environment and cancer. Cancer Causes Control 1997; 8: 529–531.

    Article  CAS  PubMed  Google Scholar 

  11. Gallagher RP, Fleshner N . Prostate cancer: 3. Individual risk factors. CMAJ 1998; 159: 807–813.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Drasch G, Schopfer J, Schrauzer GN . Selenium/cadmium ratios in human prostates: indicators of prostate cancer risk of smokers and nonsmokers, and relevance to the cancer protective effects of selenium. Biol Trace Elem Res 2005; 103: 103–107.

    Article  CAS  PubMed  Google Scholar 

  13. De Vogli R, Ferrie JE, Chandola T, Kivimaki M, Marmot MG . Unfairness and health: evidence from the Whitehall II Study. J Epidemiol Community Health 2007; 61: 513–518.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Karan D, Lin MF, Johansson SL, Batra SK . Current status of the molecular genetics of human prostatic adenocarcinomas. Int J Cancer 2003; 103: 285–293.

    Article  CAS  PubMed  Google Scholar 

  15. Isaacs WB . Molecular genetics of prostate cancer. Cancer Surv 1995; 25: 357–379.

    CAS  PubMed  Google Scholar 

  16. Vecchione A, Gottardo F, Gomella LG, Wildemore B, Fassan M, Bragantini E et al. Molecular genetics of prostate cancer: clinical translational opportunities. J Exp Clin Cancer Res 2007; 26: 25–37.

    CAS  PubMed  Google Scholar 

  17. Li LC, Okino ST, Zhao H, Pookot D, Place RF, Urakami S et al. Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci USA 2006; 103: 17337–17342.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jovanovic M, Hengartner MO . miRNAs and apoptosis: RNAs to die for. Oncogene 2006; 25: 6176–6187.

    Article  CAS  PubMed  Google Scholar 

  19. Sen CK, Roy S . miRNA: licensed to kill the messenger. DNA Cell Biol 2007; 26: 193–194.

    Article  CAS  PubMed  Google Scholar 

  20. Osada H, Takahashi T . MicroRNAs in biological processes and carcinogenesis. Carcinogenesis 2007; 28: 2–12.

    Article  CAS  PubMed  Google Scholar 

  21. Kusenda B, Mraz M, Mayer J, Pospisilova S . MicroRNA biogenesis, functionality and cancer relevance. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2006; 150: 205–215.

    Article  CAS  PubMed  Google Scholar 

  22. Wijnhoven BP, Michael MZ, Watson DI . MicroRNAs and cancer. Br J Surg 2007; 94: 23–30.

    Article  CAS  PubMed  Google Scholar 

  23. Garzon R, Fabbri M, Cimmino A, Calin GA, Croce CM . MicroRNA expression and function in cancer. Trends Mol Med 2006; 12: 580–587.

    Article  CAS  PubMed  Google Scholar 

  24. Zhang B, Pan X, Cobb GP, Anderson TA . microRNAs as oncogenes and tumor suppressors. Dev Biol 2007; 302: 1–12.

    Article  CAS  PubMed  Google Scholar 

  25. Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T . MicroRNA expression profiling in prostate cancer. Cancer Res 2007; 67: 6130–6135.

    Article  CAS  PubMed  Google Scholar 

  26. Perera FP . Environment and cancer: who are susceptible? Science 1997; 278: 1068–1073.

    Article  CAS  PubMed  Google Scholar 

  27. Hayat MJ, Howlader N, Reichman ME, Edwards BK . Cancer statistics, trends, and multiple primary cancer analyses from the Surveillance, Epidemiology, and End Results (SEER) Program. Oncologist 2007; 12: 20–37.

    Article  PubMed  Google Scholar 

  28. Kabesch M, Lauener RP . Why Old McDonald had a farm but no allergies: genes, environments, and the hygiene hypothesis. J Leukoc Biol 2004; 75: 383–387.

    Article  CAS  PubMed  Google Scholar 

  29. Strachan DP . Hay fever, hygiene, and household size. Bmj 1989; 299: 1259–1260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY et al. MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily. Proc Natl Acad Sci USA 1997; 94: 11514–11519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Condeelis J, Pollard JW . Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 2006; 124: 263–266.

    Article  CAS  PubMed  Google Scholar 

  32. De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007; 7: 256–269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Karan D, Chen SJ, Johansson SL, Singh AP, Paralkar VM, Lin MF et al. Dysregulated expression of MIC-1/PDF in human prostate tumor cells. Biochem Biophys Res Commun 2003; 305: 598–604.

    Article  CAS  PubMed  Google Scholar 

  34. Cheng I, Liu X, Plummer SJ, Krumroy LM, Casey G, Witte JS . COX2 genetic variation, NSAIDs, and advanced prostate cancer risk. Br J Cancer 2007; 97: 557–561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Wang W, Bergh A, Damber JE . Cyclooxygenase-2 expression correlates with local chronic inflammation and tumor neovascularization in human prostate cancer. Clin Cancer Res 2005; 11: 3250–3256.

    Article  CAS  PubMed  Google Scholar 

  36. Nithipatikom K, Isbell MA, Lindholm PF, Kajdacsy-Balla A, Kaul S, Campell WB . Requirement of cyclooxygenase-2 expression and prostaglandins for human prostate cancer cell invasion. Clin Exp Metastasis 2002; 19: 593–601.

    Article  CAS  PubMed  Google Scholar 

  37. Fujita H, Koshida K, Keller ET, Takahashi Y, Yoshimito T, Namiki M et al. Cyclooxygenase-2 promotes prostate cancer progression. Prostate 2002; 53: 232–240.

    Article  CAS  PubMed  Google Scholar 

  38. Luo JL, Tan W, Ricono JM, Korchynskyi O, Zhang M, Gonias SL et al. Nuclear cytokine-activated IKKalpha controls prostate cancer metastasis by repressing Maspin. Nature 2007; 446: 690–694.

    Article  CAS  PubMed  Google Scholar 

  39. Ahmad M, Rees RC, Ali SA . Escape from immunotherapy: possible mechanisms that influence tumor regression/progression. Cancer Immunol Immunother 2004; 53: 844–854.

    Article  PubMed  Google Scholar 

  40. Miller AM, Pisa P . Tumor escape mechanisms in prostate cancer. Cancer Immunol Immunother 2007; 56: 81–87.

    Article  CAS  PubMed  Google Scholar 

  41. Poggi A, Zocchi MR . Mechanisms of tumor escape: role of tumor microenvironment in inducing apoptosis of cytolytic effector cells. Arch Immunol Ther Exp 2006; 54: 323–333.

    Article  CAS  Google Scholar 

  42. Sadun RE, Sachsman SM, Chen X, Christenson KW, Morris WZ, Hu P et al. Immune signatures of murine and human cancers reveal unique mechanisms of tumor escape and new targets for cancer immunotherapy. Clin Cancer Res 2007; 13: 4016–4025.

    Article  CAS  PubMed  Google Scholar 

  43. Dupont B . Introduction: current concepts in immunity to human cancer and therapeutic antitumor vaccines. Immunol Rev 2002; 188: 5–8.

    Article  PubMed  Google Scholar 

  44. Karan D, Krieg AM, Lubaroff DM . Paradoxical enhancement of CD8 T cell-dependent anti-tumor protection despite reduced CD8 T cell responses with addition of a TLR9 agonist to a tumor vaccine. Int J Cancer 2007; 121: 1520–1528.

    Article  CAS  PubMed  Google Scholar 

  45. Baral R . Tumor vaccine: current trends in antigen specific immunotherapy. Indian J Exp Biol 2005; 43: 389–406.

    CAS  PubMed  Google Scholar 

  46. Itoh K, Hayashi A, Toh Y, Imai Y, Yamada A, Nishida T et al. Development of cancer vaccine by tumor rejection antigens. Int Rev Immunol 1997; 14: 153–171.

    Article  CAS  PubMed  Google Scholar 

  47. Saenz-Badillos J, Amin SP, Granstein RD . RNA as a tumor vaccine: a review of the literature. Exp Dermatol 2001; 10: 143–154.

    Article  CAS  PubMed  Google Scholar 

  48. Schirrmacher V . Tumor vaccine design: concepts, mechanisms, and efficacy testing. Int Arch Allergy Immunol 1995; 108: 340–344.

    Article  CAS  PubMed  Google Scholar 

  49. Dalgleish AG, Whelan MA . Cancer vaccines as a therapeutic modality: the long trek. Cancer Immunol Immunother 2006; 55: 1025–1032.

    Article  CAS  PubMed  Google Scholar 

  50. Fong L, Small EJ . Immunotherapy for prostate cancer. Curr Oncol Rep 2007; 9: 226–233.

    Article  CAS  PubMed  Google Scholar 

  51. Kaminski JM, Summers JB, Ward MB, Huber MR, Minev B . Immunotherapy and prostate cancer. Cancer Treat Rev 2003; 29: 199–209.

    Article  CAS  PubMed  Google Scholar 

  52. McNeel DG . Prostate cancer immunotherapy. Curr Opin Urol 2007; 17: 175–181.

    Article  PubMed  Google Scholar 

  53. Minev BR, Guo F, Gueorguieva I, Kaiser HE . Vaccines for immunotherapy of breast cancer and prostate cancer: new developments and comparative aspects. In Vivo 2002; 16: 405–415.

    CAS  PubMed  Google Scholar 

  54. Simons JW, Sacks N . Granulocyte-macrophage colony-stimulating factor-transduced allogeneic cancer cellular immunotherapy: the GVAX vaccine for prostate cancer. Urol Oncol 2006; 24: 419–424.

    Article  CAS  PubMed  Google Scholar 

  55. Arlen PM, Gulley JL . Therapeutic vaccines for prostate cancer: a review of clinical data. Curr Opin Investig Drugs 2005; 6: 592–596.

    CAS  PubMed  Google Scholar 

  56. Banchereau J, Fay J, Pascual V, Palucka AK . Dendritic cells: controllers of the immune system and a new promise for immunotherapy. Novartis Found Symp 2003; 252: 226–235.

    CAS  PubMed  Google Scholar 

  57. Boyd D, Hung CF, Wu TC . DNA vaccines for cancer. IDrugs 2003; 6: 1155–1164.

    CAS  PubMed  Google Scholar 

  58. Brossart P . Dendritic cells in vaccination therapies of malignant diseases. Transfus Apher Sci 2002; 27: 183–186.

    Article  PubMed  Google Scholar 

  59. Lubaroff DM, Karan D, Andrews MP, Acosta A, Abouassaly C, Sharma M et al. Decreased cytotoxic T cell activity generated by co-administration of PSA vaccine and CpG ODN is associated with increased tumor protection in a mouse model of prostate cancer. Vaccine 2006; 24: 6155–6162.

    Article  CAS  PubMed  Google Scholar 

  60. Miller G, Lahrs S, Pillarisetty VG, Shah AB, DeMatteo RP . Adenovirus infection enhances dendritic cell immunostimulatory properties and induces natural killer and T-cell-mediated tumor protection. Cancer Res 2002; 62: 5260–5266.

    CAS  PubMed  Google Scholar 

  61. Rosenberg SA, Zhai Y, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM et al. Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens. J Natl Cancer Inst 1998; 90: 1894–1900.

    Article  CAS  PubMed  Google Scholar 

  62. Xia D, Moyana T, Xiang J . Combinational adenovirus-mediated gene therapy and dendritic cell vaccine in combating well-established tumors. Cell Res 2006; 16: 241–259.

    Article  CAS  PubMed  Google Scholar 

  63. Toes RE, Offringa R, Blom RJ, Melief CJ, Kast WM . Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction. Proc Natl Acad Sci USA 1996; 93: 7855–7860.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kim JJ, Trivedi NN, Wilson DM, Mahalingam S, Morrison L, Tsai A et al. Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine. Oncogene 1998; 17: 3125–3135.

    Article  CAS  PubMed  Google Scholar 

  65. Elzey BD, Siemens DR, Ratliff TL, Lubaroff DM . Immunization with type 5 adenovirus recombinant for a tumor antigen in combination with recombinant canarypox virus (ALVAC) cytokine gene delivery induces destruction of established prostate tumors. Int J Cancer 2001; 94: 842–849.

    Article  CAS  PubMed  Google Scholar 

  66. Lubaroff DM, Konety B, Link BK, Ratliff TL, Madsen T, Shannon M et al. Clinical protocol: phase I study of an adenovirus/prostate-specific antigen vaccine in men with metastatic prostate cancer. Hum Gene Ther 2006; 17: 220–229.

    Article  CAS  PubMed  Google Scholar 

  67. Krieg AM . CpG motifs: the active ingredient in bacterial extracts? Nat Med 2003; 9: 831–835.

    Article  CAS  PubMed  Google Scholar 

  68. Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R et al. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 1995; 374: 546–549.

    Article  CAS  PubMed  Google Scholar 

  69. O'Neill L . Toll-like receptors and the danger hypothesis. Trends Immunol 2001; 22: 421.

    PubMed  Google Scholar 

  70. Takeda K, Akira S . Toll-like receptors in innate immunity. Int Immunol 2005; 17: 1–14.

    Article  CAS  PubMed  Google Scholar 

  71. Krieg AM . Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drug Discov 2006; 5: 471–484.

    Article  CAS  PubMed  Google Scholar 

  72. Vollmer J, Weeratna R, Payette P, Jurk M, Schetter C, Laucht M et al. Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities. Eur J Immunol 2004; 34: 251–262.

    Article  CAS  PubMed  Google Scholar 

  73. Krieg AM . Development of TLR9 agonists for cancer therapy. J Clin Invest 2007; 117: 1184–1194.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Carpentier A, Laigle-Donadey F, Zohar S, Capelle L, Behin A, Tibi A et al. Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma. Neuro-oncol 2006; 8: 60–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Carpentier AF, Auf G, Delattre JY . CpG-oligonucleotides for cancer immunotherapy: review of the literature and potential applications in malignant glioma. Front Biosci 2003; 8: e115–e127.

    Article  CAS  PubMed  Google Scholar 

  76. Klinman DM . Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol 2004; 4: 249–258.

    Article  CAS  PubMed  Google Scholar 

  77. Haddada H, Cordier L, Perricaudet M . Gene therapy using adenovirus vectors. Curr Top Microbiol Immunol 1995; 199: 297–306.

    CAS  PubMed  Google Scholar 

  78. Jaffe HA, Danel C, Longenecker G, Metzger M, Setoguchi Y, Rosenfeld MA et al. Adenovirus-mediated in vivo gene transfer and expression in normal rat liver. Nat Genet 1992; 1: 372–378.

    Article  CAS  PubMed  Google Scholar 

  79. Salucci V, Mennuni C, Calvaruso F, Cerino R, Neuner P, Ciliberto G et al. CD8+ T-cell tolerance can be broken by an adenoviral vaccine while CD4+ T-cell tolerance is broken by additional co-administration of a Toll-like receptor ligand. Scand J Immunol 2006; 63: 35–41.

    Article  CAS  PubMed  Google Scholar 

  80. Wingender G, Garbi N, Schumak B, Jungerkes F, Endl E, von Bubnoff D et al. Systemic application of CpG-rich DNA suppresses adaptive T cell immunity via induction of IDO. Eur J Immunol 2006; 36: 12–20.

    Article  CAS  PubMed  Google Scholar 

  81. Mellor AL, Baban B, Chandler PR, Manlapat A, Kahler DJ, Munn DH . Cutting edge: CpG oligonucleotides induce splenic CD19+ dendritic cells to acquire potent indoleamine 2,3-dioxygenase-dependent T cell regulatory functions via IFN Type 1 signaling. J Immunol 2005; 175: 5601–5605.

    Article  CAS  PubMed  Google Scholar 

  82. Offringa R . Cancer immunotherapy is more than a numbers game. Science 2006; 314: 68–69.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

DK is supported by the grant from Veterans Affairs Medical Center. We thank Kristina Greiner (University of Iowa) for editing the Manuscript.

Author information

Authors and Affiliations

  1. Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA

    D Karan & J B Thrasher

  2. Cancer Research Unit, VA Medical Center, Kansas City, MO, USA

    D Karan & J B Thrasher

  3. Departments of Urology, and Microbiology, University of Iowa, Iowa City, IA, USA

    D Lubaroff

Authors
  1. D Karan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J B Thrasher
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Lubaroff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Karan.

Additional information

Disclosure

Authors have no financial conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karan, D., Thrasher, J. & Lubaroff, D. Prostate cancer: genes, environment, immunity and the use of immunotherapy. Prostate Cancer Prostatic Dis 11, 230–236 (2008). https://doi.org/10.1038/pcan.2008.3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/pcan.2008.3

Keywords

This article is cited by

Search

Advanced search

Quick links