Seminars in Oncology
Volume 34, Issue 2 , Pages 165-172 , April 2007

Immunotherapeutic Strategies for High-Risk Bladder Cancer

  • Padmanee Sharma

      Affiliations

    • Department of Genitourinary Medical Oncology and Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
    • Corresponding Author InformationAddress correspondence to Padmanee Sharma, MD, PhD, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1374, Houston, TX 77030.
    • ,
  • Lloyd J. Old

      Affiliations

    • Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY.
    • ,
  • James P. Allison

      Affiliations

    • Howard Hughes Medical Institute and Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY.

References 

  1. Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas (With a report of ten original cases). Am J Med Sci. 1893;105:487–511
  2. Old LJ. Effect of Bacillus Calmette-Guerin (B.C.G) infection on transplanted tumours in the mouse. Nature. 1959;184:291–292
  3. Janeway CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216
  4. Hemmi H, Takeuchi O, Kawai T, et al. A toll-like receptor recognizes bacterial DNA. Nature. 2000;408:740–745
  5. Brightbill HD, Libraty DH, Krutzik SR, et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science. 1999;285:732–736
  6. Tsuji S, Matsumoto M, Takeuchi O, et al. Maturation of human dendritic cells by cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guerin: Involvement of toll-like receptors. Infect Immun. 2000;68:6883–6890
  7. de Boer EC, Somogyi L, de Ruiter GJ, et al. Role of interleukin-8 in onset of the immune response in intravesical BCG therapy for superficial bladder cancer. Urol Res. 1997;25:31–34
  8. Thalmann GN, Sermier A, Rentsch C, et al. Urinary interleukin-8 and 18 predict the response of superficial bladder cancer to intravesical therapy with bacillus Calmette-Guerin. J Urol. 2000;164:2129–2133
  9. Jackson AM, Alexandroff AB, Kelly RW, et al. Changes in urinary cytokines and soluble intercellular adhesion molecule-1 (ICAM-1) in bladder cancer patients after bacillus Calmette-Guerin (BCG) immunotherapy. Clin Exp Immunol. 1995;99:369–375
  10. Prescott S, James K, Hargreave TB, et al. Radio-immunoassay detection of interferon-gamma in urine after intravesical Evans BCG therapy. J Urol. 1990;144:1248–1251
  11. Haaff EO, Catalona WJ, Ratliff TL. Detection of interleukin 2 in the urine of patients with superficial bladder tumors after treatment with intravesical BCG. J Urol. 1986;136:970–974
  12. De Boer EC, De Jong WH, Steerenberg PA, et al. Induction of urinary interleukin-1 (IL-1), IL-2, IL-6, and tumour necrosis factor during intravesical immunotherapy with bacillus Calmette-Guerin in superficial bladder cancer. Cancer Immunol Immunother. 1992;34:306–312
  13. Bohle A, Gerdes J, Ulmer AJ, et al. Effects of local bacillus Calmette-Guerin therapy in patients with bladder carcinoma on immunocompetent cells of the bladder wall. J Urol. 1990;144:53–58
  14. de Boer EC, de Jong WH, van der Meijden AP, et al. Leukocytes in the urine after intravesical BCG treatment for superficial bladder cancer (A flow cytofluorometric analysis). Urol Res. 1991;19:45–50
  15. Sharma P, Jungbluth A, Gnjatic S, et al: CD8+ tumor-infiltrating lymphocytes as a statistically significant marker of disease recurrence and survival in transitional cell carcinoma patients. Proc Natl Acad Sci USA (in press)
  16. Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203–213
  17. Schumacher K, Haensch W, Roefzaad C, et al. Prognostic significance of activated CD8(+) T cell infiltrations within esophageal carcinomas. Cancer Res. 2001;61:3932–3936
  18. Naito Y, Saito K, Shiiba K, et al. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res. 1998;58:3491–3494
  19. Huntington ND, Tarlinton DM. CD45: Direct and indirect government of immune regulation. Immunol Lett. 2004;94:167–174
  20. Palacios EH, Weiss A. Function of the Src-family kinases, Lck and Fyn, in T cell development and activation. Oncogene. 2004;23:7990–8000
  21. Tomiyama H, Takata H, Matsuda T, et al. Phenotypic classification of human CD8+ Tcells reflecting their function: Inverse correlation between correlation between quantitative expression of CD27 and cytotoxic effector function. Eur J Immunol. 2004;34:999–1010
  22. Korman AJ, Peggs KS, Allison JP. Checkpoint blockade in cancer immunotherapy. Adv Immunol. 2006;90:293–335
  23. Walunas TL, Lenschow DJ, Bakker CY, et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity. 1994;1:405–413
  24. Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med. 1995;182:459–465
  25. Chambers CA, Sullivan TJ, Allison JP. Lymphoproliferation in CTLA-4-deficient mice is mediated by costimulation-dependent activation of CD4+ T cells. Immunity. 1997;7:885–895
  26. Tivol EA, Borriello F, Schweitzer AN, et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 1995;3:541–547
  27. Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4. Science. 1995;270:985–988
  28. Davis SJ, Ikemizu S, Evans EJ, et al. The nature of molecular recognition by T cells. Nat Immunol. 2003;4:217–224
  29. Chambers C, Kuhns M, Egen J, et al. CTLA-4 mediated inhibition in regulation of T cell responses: Mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol. 2001;19:565–594
  30. van der Bruggen P, Traversari C, Chomez P, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991;254:1643–1647
  31. Boel P, Wildmann C, Sensi ML, et al. BAGE: A new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity. 1995;2:167–175
  32. Van den Eynde B, Peeters O, De Backer O, et al. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med. 1995;182:689–698
  33. Sahin U, Tureci O, Schmitt H, et al. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A. 1995;92:11810–11813
  34. Chen TY, Scanlan MJ, Sahin U, et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci U S A. 1997;94:1914–1918
  35. Scanlan MJ, Simpson AJ, Old LJ. The cancer/testis genes: Review, standardization, and commentary. Cancer Immun. 2004;4:1
  36. Stockert E, Jager E, Chen YT, et al. A survey of the humoral immune response of cancer patients to a panel of human tumor antigens. J Exp Med. 1998;87:1349–1354
  37. Jager E, Nagata Y, Gnjatic S, et al. Monitoring CD8 T cell responses to NY-ESO-1: Correlation of humoral and cellular immune responses. Proc Natl Acad Sci U S A. 2000;97:4760–4765
  38. Valmori D, Dutoit V, Lienard D, et al. Naturally occurring human lymphocyte antigen-A2 restricted CD8+ T cell response to the cancer testis antigen NY-ESO-1 in melanoma patients. Cancer Res. 2000;60:4499–4506
  39. Yamaguchi H, Tanaka F, Ohta M, et al. Identification of HLA-A24-restricted CTL epitope from cancer-testis antigen, NY-ESO-1, and induction of a specific antitumor immune response. Clin Cancer Res. 2004;10:890–896
  40. Zarour HM, Storkus WJ, Brusic V, et al. NY-ESO-1 encodes DRB1*0401-restricted epitopes recognized by melanoma-reactive CD4+ T cells. Cancer Res. 2000;60:4946–4952
  41. Jager E, Jager D, Karbach J, et al. Identification of NY-ESO-1 epitopes presented by human histocompatibility antigen (HLA)-DRB4*0101-0103 and recognized by CD4(+) T lymphocytes of patients with NY-ESO-1-expressing melanoma. J Exp Med. 2000;191:625–630
  42. Chen YT, Boyer AD, Viars CS, et al. Genomic cloning and localization of CTAG, a gene encoding an autoimmunogenic cancer-testis antigen NY-ESO-1, to human chromosome Xq28. Cytogenet Cell Genet. 1997;79:237–240
  43. Lethe B, Lucas S, Michaux L, et al. LAGE-1, a new gene with tumor specificity. Int J Cancer. 1998;76:903–908
  44. Sharma P, Gnjatic S, Jungbluth AA, et al. Frequency of NY-ESO-1 and LAGE-1 expression in bladder cancer and evidence of a new NY-ESO-1 T cell epitope in a patient with bladder cancer. Cancer Immun. 2003;3:19
  45. Sharma P, Shen Y, Wen S, et al. Cancer testis antigens: Expression and correlation with survival in human urothelial carcinoma. Clin Cancer Res. 2006;12:5442–5447
  46. Condon C, Watkins SC, Celluzzi CM, et al. DNA-based immunization by in vivo transfection of dendritic cells. Nat Med. 1996;2:1122–1128
  47. Doe B, Selby M, Barnett S, et al. Induction of cytotoxic T lymphocytes by intramuscular immunization with plamid DNA is facilitated by bone marrow-derived cells. Proc Natl Acad Sci U S A. 1996;93:8578–8583
  48. Nishiyama T, Tachibana M, Horiguchi Y, et al. Immunotherapy of bladder cancer using autologous dendritic cells pulsed with human lymphocyte antigen-A24-specific MAGE-3 peptide. Clin Cancer Res. 2001;7:23–31
  49. Marchand M, Punt CJ, Aamdal S, et al. Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: A clinical report. Eur J Cancer. 2003;39:70–77
  50. Caton AJ, Cozzo C, Larkin J, et al. CD4+ CD25+ regulatory T cell selection. Ann NY Acad Sci. 2004;1029:101–114
  51. Jordan MS, Boesteanu A, Reed AJ, et al. Thymic selection of CD4+ CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol. 2001;2:301–306
  52. Salomon B, Lenschow DJ, Rhee L, et al. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity. 2000;12:431–440
  53. Sakaguchi S. Regulatory T cells: Mediating compromises between host and parasite. Nat Immunol. 2003;4:10–11
  54. Roncarolo MG, Bacchetta R, Bordignon C, et al. Type I T regulatory cells. Immunol Rev. 2001;182:68–79
  55. Shimizu J, Yamazaki S, Sakaguchi S. Introduction of tumor immunity by removing CD25+CD4+ T cells: A common basis between tumor immunity and autoimmunity. J Immunol. 1999;163:5211–5218
  56. Onizuka S, Tawara I, Shimizu J, et al. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res. 1999;59:3128–3133
  57. Sutmuller RP, van Duivenvoorde LM, van Elsas A, et al. Synergism of cytotoxic T lymphocyte responses. J Exp Med. 2001;194:823–832
  58. Golgher D, Jones E, Powrie F, et al. Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens. Eur J Immunol. 2002;32:3267–3275
  59. Gray CP, Arosio P, Hersey P. Association of increase levels of heavy-chain ferritin with increased CD4+ CD25+ regulatory T cell levels in patients with melanoma. Clin Cancer Res. 2003;9:2551–2559
  60. Marshall NA, Christie LE, Munro LR, et al. Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood. 2004;103:1755–1762
  61. Woo Ey, Chu CS, Goletz TJ, 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 Res. 2001;611:4766–4772
  62. Woo EY, Yeh H, Chu CS, et al. Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J Immunol. 2002;168:4272–4276
  63. Ichihara F, Kono K, Takahashi A, et al. Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers. Clin Cancer Res. 2003;9:4404–4408
  64. Sasada T, Kimura M, Yoshida Y, et al. CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies: Possible involvement of regulatory T cells in disease progression. Cancer. 2003;98:1089–1099
  65. Wolf AM, Wolf D, Steurer M, et al. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res. 2003;9:606–612
  66. Liyanage UK, Moore TT, Joo HG, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002;169:2756–2761
  67. Thornton AM, Shevach EM. Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J Immunol. 2000;164:183–190
  68. Baecher-Allan C, Viglietta V, Hafler DA. Inhibition of human CD4(+)CD25(+high) regulatory T cell function. J Immunol. 2002;169:6210–6217
  69. Pasare C, Medzhitov R. Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science. 2003;299:1033–1036
  70. Yang Y, Huang CT, Huang X, et al. Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance. Nat Immunol. 2004;5:508–515
  71. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271:1734–1736
  72. Yang YF, Zou JP, Mu J, et al. Enhanced induction of antitumor T cell responses by cytotoxic T lymphocyte-associated molecule-4 blockade: The effect is manifested only at the restricted tumor-bearing stages. Cancer Res. 1997;57:4036–4041
  73. Ryan MH, Bristol JA, McDuffie E, et al. Regression of extensive pulmonary metastases in mice by adoptive transfer of antigen-specific CD8+ CTL reactive against tumor cells expressing a naturally occurring rejection epitope. J Immunol. 2001;167:4286–4292
  74. van Elsas A, Hurwitz AA, Allison JP. 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. 1999;190:355–366
  75. van Elsas A, Sutmuller RP, Hurwitz AA, et al. Elucidating the autoimmune and antitumor effector mechanisms of a treatment based on cytotoxic T lymphocyte antigen-4 blockade in combination with a B16 melanoma vaccine: Comparison of prophylaxis and therapy. J Exp Med. 2001;194:481–489
  76. Hodi FS, Mihm MC, Soiffer RJ, et al. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci U S A. 2003;100:4712–4717
  77. Phan GQ, Yang JC, Sherry RM, et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A. 2003;100:8372–8377

 Supported in part by the UTMDACC Bladder Cancer SPORE Career Development Award 5P50 CA091846 04 (PP-CDP4), Physician Scientist Program Award and Institutional Research Grant (P. Sharma).

PII: S0093-7754(06)00481-7

doi: 10.1053/j.seminoncol.2006.12.004

Seminars in Oncology
Volume 34, Issue 2 , Pages 165-172 , April 2007

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