The impact of T-cell immunity on ovarian cancer outcomes

Immunological Reviews

Volumn 222, Issue 1, 2008, Pages 101-116

  Nelson, Brad H ^a  

^a BRITISH COLUMBIA CANCER AGENCY   (Canada)

Author keywords

Ascites; Cytokines; Effector T cells; Immunotherapy; Ovarian cancer; Prognosis; Regulatory T cells

Indexed keywords

AUTOANTIBODY; BRCA1 PROTEIN; BRCA2 PROTEIN; CARBOPLATIN; CELL SURFACE PROTEIN; CISPLATIN; CXCL9 CHEMOKINE; CYCLOPHOSPHAMIDE; DOCETAXEL; GAMMA INTERFERON; INTERLEUKIN 2; MACROPHAGE DERIVED CHEMOKINE; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 1; PACLITAXEL; PROTEIN PD L1; PROTEIN PD L2; SECONDARY LYMPHOID TISSUE CHEMOKINE; TAXANE DERIVATIVE; TRANSCRIPTION FACTOR FOXP3; TUMOR ANTIGEN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VASCULOTROPIN;

CANCER CHEMOTHERAPY; CANCER RECURRENCE; CANCER RISK; CANCER STAGING; CANCER SURVIVAL; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL INFILTRATION; CELLULAR IMMUNITY; CLINICAL FEATURE; CYTOREDUCTIVE SURGERY; CYTOTOXICITY; HUMAN; IMMUNE SYSTEM; IMMUNOHISTOCHEMISTRY; LYMPHOCYTOPENIA; MUTATIONAL ANALYSIS; NONHUMAN; OUTCOME ASSESSMENT; OVARY CARCINOMA; PRIORITY JOURNAL; PROGNOSIS; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; REVIEW; T LYMPHOCYTE; TH1 CELL; TUMOR ASSOCIATED LEUKOCYTE; TUMOR IMMUNITY;

ANTIGENS, CD; ANTIGENS, CD3; ANTIGENS, CD8; APOPTOSIS REGULATORY PROTEINS; CLINICAL TRIALS AS TOPIC; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; IMMUNITY, CELLULAR; IMMUNOTHERAPY; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; LYMPHOCYTES, TUMOR-INFILTRATING; MUCIN-1; NEOPLASM RECURRENCE, LOCAL; OVARIAN NEOPLASMS; T-LYMPHOCYTES, REGULATORY; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL;

EID: 41149148789     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.1600-065X.2008.00614.x     Document Type: Review

References (202)

1. Gilks CB. Subclassification of ovarian surface epithelial tumors based on correlation of histologic and molecular pathologic data. Int J Gynecol Pathol 2004 23 : 200 205.
2. Geisler JP, Hatterman-Zogg MA, Rathe JA, Buller RE. Frequency of BRCA1 dysfunction in ovarian cancer. J Natl Cancer Inst 2002 94 : 61 67.
3. Hilton JL, Geisler JP, Rathe JA, Hattermann-Zogg MA, DeYoung B, Buller RE. Inactivation of BRCA1 and BRCA2 in ovarian cancer. J Natl Cancer Inst 2002 94 : 1396 1406.
4. Bookman MA. Standard treatment in advanced ovarian cancer in 2005: the state of the art. Int J Gynecol Cancer 2005 15 (Suppl) : 212 220.
5. Ozols RF, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic oncology group study. J Clin Oncol 2003 21 : 3194 3200.
6. du Bois A, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 2003 95 : 1320 1329.
7. Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol 2000 19 : 3 10.
8. Ozols RF. Management of advanced ovarian cancer consensus summary. Advanced Ovarian Cancer Consensus Faculty. Semin Oncol 2000 27 (Suppl.) : 47 49.
9. Jass JR. Lymphocytic infiltration and survival in rectal cancer. J Clin Pathol 1986 39 : 585 589.
10. Clemente CG, Mihm MC Jr., Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 1996 77 : 1303 1310.
11. Halpern AC, Schuchter LM. Prognostic models in melanoma. Semin Oncol 1997 24 (Suppl.) : S2 S7.
12. Diederichsen AC, Hjelmborg JB, Christensen PB, Zeuthen J, Fenger C. Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells. Cancer Immunol Immunother 2003 52 : 423 428.
13. Vesalainen S, Lipponen P, Talja M, Syrjanen K. Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur J Cancer 1994 30A : 1797 1803.
14. Marrogi AJ, et al. Study of tumor infiltrating lymphocytes and transforming growth factor-beta as prognostic factors in breast carcinoma. Int J Cancer 1997 74 : 492 501.
15. Naito Y, et al. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 1998 58 : 3491 3494.
16. Schumacher K, Haensch W, Roefzaad C, Schlag PM. Prognostic significance of activated CD8(+) T cell infiltrations within esophageal carcinomas. Cancer Res 2001 61 : 3932 3936.
17. Nakano O, et al. Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res 2001 61 : 5132 5136.
18. Galon J, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006 313 : 1960 1964.
19. Zhang L, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003 348 : 203 213.
20. Shen GH, et al. Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma. Br J Cancer 2000 83 : 196 203.
21. Chen CA, et al. Serum vascular endothelial growth factor in epithelial ovarian neoplasms: correlation with patient survival. Gynecol Oncol 1999 74 : 235 240.
22. Hartenbach EM, et al. Vascular endothelial growth factor (VEGF) expression and survival in human epithelial ovarian carcinomas. Cancer Lett 1997 121 : 169 175.
23. Raspollini MR, et al. Tumour-infiltrating gamma/delta T-lymphocytes are correlated with a brief disease-free interval in advanced ovarian serous carcinoma. Ann Oncol 2005 16 : 590 596.
24. Tomsova M, Melichar B, Sedlakova I, Steiner I. Prognostic significance of CD3+ tumor-infiltrating lymphocytes in ovarian carcinoma. Gynecol Oncol 2008 108 : 415 420.
25. Woo EY, 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 61 : 4766 4772.
26. Curiel TJ, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004 10 : 942 949.
27. Wolf D, et al. The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 2005 11 : 8326 8331.
28. Sato E, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 2005 102 : 18538 18543.
29. Hamanishi J, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci USA 2007 104 : 3360 3365.
30. Keir ME, Francisco LM, Sharpe AH. PD-1 and its ligands in T-cell immunity. Curr Opin Immunol 2007 19 : 309 314.
31. Curiel TJ, et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 2003 9 : 562 567.
32. Blank C, Mackensen A. Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother 2007 56 : 739 745.
33. Bamias A, et al. Significant differences of lymphocytes isolated from ascites of patients with ovarian cancer compared to blood and tumor lymphocytes. Association of CD3(+)CD56(+) cells with platinum resistance. Gynecol Oncol 2007 106 : 75 81.
34. Linn YC, Hui KM. Cytokine-induced killer cells: NK-like T cells with cytotolytic specificity against leukemia. Leuk Lymphoma 2003 44 : 1457 1462.
35. Bamias A, et al. Correlation of NK T-like CD3+CD56+ cells and CD4+CD25+(hi) regulatory T cells with VEGF and TNFalpha in ascites from advanced ovarian cancer: association with platinum resistance and prognosis in patients receiving first-line, platinum-based chemotherapy. Gynecol Oncol 2008 108 : 421 427.
36. Marth C, et al. Interferon-gamma expression is an independent prognostic factor in ovarian cancer. Am J Obstet Gynecol 2004 191 : 1598 1605.
37. Kusuda T, Shigemasa K, Arihiro K, Fujii T, Nagai N, Ohama K. Relative expression levels of Th1 and Th2 cytokine mRNA are independent prognostic factors in patients with ovarian cancer. Oncol Rep 2005 13 : 1153 1158.
38. Akahiro J, Konno R, Ito K, Okamura K, Yaegashi N. Impact of serum interleukin-18 level as a prognostic indicator in patients with epithelial ovarian carcinoma. Int J Clin Oncol 2004 9 : 42 46.
39. Zeimet AG, et al. Ascitic interleukin-12 is an independent prognostic factor in ovarian cancer. J Clin Oncol 1998 16 : 1861 1868.
40. Berek JS, Chung C, Kaldi K, Watson JM, Knox RM, Martinez-Maza O. Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer. Am J Obstet Gynecol 1991 164 : 1038 1042 discussion 1042-1043.
41. Scambia G, et al. Prognostic significance of interleukin 6 serum levels in patients with ovarian cancer. Br J Cancer 1995 71 : 354 356.
42. Scambia G, et al. Interleukin-6 serum levels in patients with gynecological tumors. Int J Cancer 1994 57 : 318 323.
43. Tempfer C, Zeisler H, Sliutz G, Haeusler G, Hanzal E, Kainz C. Serum evaluation of interleukin 6 in ovarian cancer patients. Gynecol Oncol 1997 66 : 27 30.
44. Garg R, et al. Common polymorphism in interleukin 6 influences survival of women with ovarian and peritoneal carcinoma. Gynecol Oncol 2006 103 : 793 796.
45. Jiang YP, Wu XH, Shi B, Wu WX, Yin GR. Expression of chemokine CXCL12 and its receptor CXCR4 in human epithelial ovarian cancer: an independent prognostic factor for tumor progression. Gynecol Oncol 2006 103 : 226 233.
46. Rolland P, Deen S, Scott I, Durrant L, Spendlove I. Human leukocyte antigen class I antigen expression is an independent prognostic factor in ovarian cancer. Clin Cancer Res 2007 13 : 3591 3596.
47. Moore DH, Fowler WC Jr., Olafsson K. Class I histocompatibility antigen expression: a prognostic factor for aneuploid ovarian cancers. 1990 38 : 458 461.
48. Gamzatova Z, et al. Human leucocyte antigen (HLA) A2 as a negative clinical prognostic factor in patients with advanced ovarian cancer. Gynecol Oncol 2006 103 : 145 150.
49. Monos DS, et al. Identification of HLA-DQalpha and -DRbeta residues associated with susceptibility and protection to epithelial ovarian cancer. Hum Immunol 2005 66 : 554 562.
50. Tamiolakis D, Kotini A, Venizelos J, Jivannakis T, Simopoulos C, Papadopoulos N. Prognostic significance of HLA-DR antigen in serous ovarian tumors. Clin Exp Med 2003 3 : 113 118.
51. Matsushita N, Ghazizadeh M, Konishi H, Araki T. Association of ovarian tumor epithelium coexpressing HLA-DR and CA-125 antigens with tumor infiltrating cytotoxic T lymphocytes. J Nippon Med Sch 2003 70 : 40 44.
52. Rangel LB, et al. Anomalous expression of the HLA-DR alpha and beta chains in ovarian and other cancers. Cancer Biol Ther 2004 3 : 1021 1027.
53. Sharma S, et al. A-kinase anchoring protein 3 messenger RNA expression correlates with poor prognosis in epithelial ovarian cancer. Gynecol Oncol 2005 99 : 183 188.
54. Tammela J, et al. SCP-1 cancer/testis antigen is a prognostic indicator and a candidate target for immunotherapy in epithelial ovarian cancer. Cancer Immun 2004 4 : 10.
55. Dong HP, et al. NK- and B-cell infiltration correlates with worse outcome in metastatic ovarian carcinoma. Am J Clin Pathol 2006 125 : 451 458.
56. Eisenthal A, Polyvkin N, Bramante-Schreiber L, Misonznik F, Hassner A, Lifschitz-Mercer B. Expression of dendritic cells in ovarian tumors correlates with clinical outcome in patients with ovarian cancer. Hum Pathol 2001 32 : 803 807.
57. Bishara S, et al. Pre-treatment white blood cell subtypes as prognostic indicators in ovarian cancer. Eur J Obstet Gynecol Reprod Biol 2008 in press.
58. Toy EP, Chambers JT, Kacinski BM, Flick MB, Chambers SK. The activated macrophage colony-stimulating factor (CSF-1) receptor as a predictor of poor outcome in advanced epithelial ovarian carcinoma. Gynecol Oncol 2001 80 : 194 200.
59. Kryczek I, et al. Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res 2007 67 : 8900 8905.
60. Kryczek I, et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 2006 203 : 871 881.
61. Stone B, et al. Serologic analysis of ovarian tumor antigens reveals a bias toward antigens encoded on 17q. Int J Cancer 2003 104 : 73 84.
62. Goodell V, et al. Antibody immunity to the p53 oncogenic protein is a prognostic indicator in ovarian cancer. J Clin Oncol 2006 24 : 762 768.
63. Vogl FD, Frey M, Kreienberg R, Runnebaum IB. Autoimmunity against p53 predicts invasive cancer with poor survival in patients with an ovarian mass. Br J Cancer 2000 83 : 1338 1343.
64. Mayerhofer K, et al. Humoral p53 antibody response is a prognostic parameter in ovarian cancer. Anticancer Res 1999 19 : 875 878.
65. Hogdall EV, et al. P53 autoantibodies in sera from Danish ovarian cancer patients and their correlation with clinical data and prognosis. Apmis 2002 110 : 545 553.
66. Gadducci A, et al. Assessment of the prognostic relevance of serum anti-p53 antibodies in epithelial ovarian cancer. 1999 72 : 76 81.
67. Cramer DW, et al. Conditions associated with antibodies against the tumor-associated antigen MUC1 and their relationship to risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev 2005 14 : 1125 1131.
68. Terry KL, Titus-Ernstoff L, McKolanis JR, Welch WR, Finn OJ, Cramer DW. Incessant ovulation, mucin 1 immunity, and risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev 2007 16 : 30 35.
69. Surowiak P, et al. CD46 expression is indicative of shorter revival-free survival for ovarian cancer patients. Anticancer Res 2006 26 : 4943 4948.
70. Wei S, et al. Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma. Cancer Res 2005 65 : 5020 5026.
71. Schroder W, Vering A, Stegmuller M, Strohmeier R. Lymphocyte subsets in patients with ovarian and breast cancer. Eur J Gynaecol Oncol 1997 18 : 474 477.
72. Papadopoulos N, et al. Gains and losses of CD8, CD20 and CD56 expression in tumor stroma-infiltrating lymphocytes compared with tumor-associated lymphocytes from ascitic fluid and lymphocytes from tumor draining lymph nodes in serous papillary ovarian carcinoma patients. Eur J Gynaecol Oncol 2002 23 : 533 536.
73. Santin AD, et al. Phenotypic and functional analysis of tumor-infiltrating lymphocytes compared with tumor-associated lymphocytes from ascitic fluid and peripheral blood lymphocytes in patients with advanced ovarian cancer. Gynecol Obstet Invest 2001 51 : 254 261.
74. Chen J, Niu H, He W, Ba D. Antitumor activity of expanded human tumor-infiltrating gammadelta T lymphocytes. Int Arch Allergy Immunol 2001 125 : 256 263.
75. Qi J, Zhang J, Zhang S, Cui L, He W. Immobilized MICA could expand human Vdelta1 gammadelta T cells in vitro that displayed major histocompatibility complex class I chain-related A-dependent cytotoxicity to human epithelial carcinomas. Scand J Immunol 2003 58 : 211 220.
76. Knutson KL, Disis ML. Clonal diversity of the T-cell population responding to a dominant HLA-A2 epitope of HER-2/neu after active immunization in an ovarian cancer patient. Hum Immunol 2002 63 : 547 557.
77. Peng G, Wang HY, Peng W, Kiniwa Y, Seo KH, Wang RF. Tumor-infiltrating gammadelta T cells suppress T and dendritic cell function via mechanisms controlled by a unique toll-like receptor signaling pathway. Immunity 2007 27 : 334 348.
78. Hayashi K, et al. Clonal expansion of T cells that are specific for autologous ovarian tumor among tumor-infiltrating T cells in humans. Gynecol Oncol 1999 74 : 86 92.
79. Pappas J, et al. Substantial proportions of identical beta-chain T-cell receptor transcripts are present in epithelial ovarian carcinoma tumors. Cell Immunol 2005 234 : 81 101.
80. Halapi E, et al. Restricted T cell receptor V-beta and J-beta usage in T cells from interleukin-2-cultured lymphocytes of ovarian and renal carcinomas. Cancer Immunol Immunother 1993 36 : 191 197.
81. Peoples GE, Davey MP, Goedegebuure PS, Schoof DD, Eberlein TJ. T cell receptor V beta 2 and V beta 6 mediate tumor-specific cytotoxicity by tumor-infiltrating lymphocytes in ovarian cancer. J Immunol 1993 151 : 5472 5480.
82. Peoples GE, Yoshino I, Douville CC, Andrews JV, Goedegebuure PS, Eberlein TJ. TCR V beta 3+ and V beta 6+ CTL recognize tumor-associated antigens related to HER2/neu expression in HLA-A2+ ovarian cancers. J Immunol 1994 152 : 4993 4999.
83. Kooi S, Freedman RS, Rodriguez-Villanueva J, Platsoucas CD. Cytokine production by T-cell lines derived from tumor-infiltrating lymphocytes from patients with ovarian carcinoma: tumor-specific immune responses and inhibition of antigen-independent cytokine production by ovarian tumor cells. Lymphokine Cytokine Res 1993 12 : 429 437.
84. Goedegebuure PS, et al. Simultaneous production of T helper-1-like cytokines and cytolytic activity by tumor-specific T cells in ovarian and breast cancer. Cell Immunol 1997 175 : 150 156.
85. Nash MA, et al. Differential expression of cytokine transcripts in human epithelial ovarian carcinoma by solid tumour specimens, peritoneal exudate cells containing tumour, tumour-infiltrating lymphocyte (TIL)-derived T cell lines and established tumour cell lines. Clin Exp Immunol 1998 112 : 172 180.
86. Dadmarz RD, et al. Tumor-infiltrating lymphocytes from human ovarian cancer patients recognize autologous tumor in an MHC class II-restricted fashion. Cancer J Sci Am 1996 2 : 263 272.
87. Melichar B, Nash MA, Lenzi R, Platsoucas CD, Freedman RS. Expression of costimulatory molecules CD80 and CD86 and their receptors CD28, CTLA-4 on malignant ascites CD3+ tumour-infiltrating lymphocytes (TIL) from patients with ovarian and other types of peritoneal carcinomatosis. Clin Exp Immunol 2000 119 : 19 27.
88. Santin AD, et al. Restoration of tumor specific human leukocyte antigens class I-restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer. Int J Gynecol Cancer 2004 14 : 64 75.
89. Ioannides CG, Freedman RS, Platsoucas CD, Rashed S, Kim YP. Cytotoxic T cell clones isolated from ovarian tumor-infiltrating lymphocytes recognize multiple antigenic epitopes on autologous tumor cells. J Immunol 1991 146 : 1700 1707.
90. Ioannides CG, Platsoucas CD, Rashed S, Wharton JT, Edwards CL, Freedman RS. Tumor cytolysis by lymphocytes infiltrating ovarian malignant ascites. Cancer Res 1991 51 : 4257 4265.
91. Lockhart DC, et al. Loss of T-cell receptor-CD3zeta and T-cell function in tumor-infiltrating lymphocytes but not in tumor-associated lymphocytes in ovarian carcinoma. Surgery 2001 129 : 749 756.
92. Rabinowich H, et al. Expression of cytokine genes or proteins and signaling molecules in lymphocytes associated with human ovarian carcinoma. Int J Cancer 1996 68 : 276 284.
93. Chen CK, Wu MY, Chao KH, Ho HN, Sheu BC, Huang SC. T lymphocytes and cytokine production in ascitic fluid of ovarian malignancies. J Formos Med Assoc 1999 98 : 24 30.
94. Engel H, et al. Detection of chromosomal aberrations in tumor cells and tumor infiltrating lymphocytes by molecular cytogenetics in patients with gynecological cancer. Cancer Genet Cytogenet 1998 106 : 159 165.
95. Peoples GE, Schoof DD, Andrews JV, Goedegebuure PS, Eberlein TJ. T-cell recognition of ovarian cancer. Surgery 1993 114 : 227 234.
96. Peoples GE, Goedegebuure PS, Andrews JV, Schoof DD, Eberlein TJ. HLA-A2 presents shared tumor-associated antigens derived from endogenous proteins in ovarian cancer. J Immunol 1993 151 : 5481 5491.
97. Freedman RS, Platsoucas CD. Immunotherapy for peritoneal ovarian carcinoma metastasis using ex vivo expanded tumor infiltrating lymphocytes. Cancer Treat Res 1996 82 : 115 146.
98. Hellstrom I, Goodman G, Pullman J, Yang Y, Hellstrom KE. Overexpression of HER-2 in ovarian carcinomas. Cancer Res 2001 61 : 2420 2423.
99. Peethambaram PP, et al. Her-2/neu expression in ovarian cancer: pre- and postexposure to platinum chemotherapy. Gynecol Oncol 2003 89 : 99 104.
100. Nijman HW, et al. T cell infiltration and MHC I and II expression in the presence of tumor antigens: an immunohistochemical study in patients with serous epithelial ovarian cancer. Eur J Obstet Gynecol Reprod Biol 2001 94 : 114 120.
101. Tuefferd M, et al. HER2 status in ovarian carcinomas: a Multicenter Gineco study of 320 patients. PLoS ONE 2007 2 : e1138.
102. Gritzapis AD, Perez SA, Baxevanis CN, Papamichail M. Pooled peptides from HER-2/neu-overexpressing primary ovarian tumours induce CTL with potent antitumour responses in vitro and in vivo. Br J Cancer 2005 92 : 72 79.
103. Fisk B, et al. Existent proliferative responses of peripheral blood mononuclear cells from healthy donors and ovarian cancer patients to HER-2 peptides. Anticancer Res 1997 17 : 45 53.
104. Okugawa T, et al. A novel human HER2-derived peptide homologous to the mouse K(d)-restricted tumor rejection antigen can induce HLA-A24-restricted cytotoxic T lymphocytes in ovarian cancer patients and healthy individuals. Eur J Immunol 2000 30 : 3338 3346.
105. Disis ML, Knutson KL, Schiffman K, Rinn K, McNeel DG. Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer. Breast Cancer Res Treat 2000 62 : 245 252.
106. Baxevanis CN, Gritzapis AD, Tsitsilonis OE, Katsoulas HL, Papamichail M. HER-2/neu-derived peptide epitopes are also recognized by cytotoxic CD3(+)CD56(+) (natural killer T) lymphocytes. Int J Cancer 2002 98 : 864 872.
107. Yoshino I, Peoples GE, Goedegebuure PS, Maziarz R, Eberlein TJ. Association of HER2/neu expression with sensitivity to tumor-specific CTL in human ovarian cancer. J Immunol 1994 152 : 2393 2400.
108. Peoples GE, Goedegebuure PS, Smith R, Linehan DC, Yoshino I, Eberlein TJ. Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proc Natl Acad Sci USA 1995 92 : 432 436.
109. Linehan DC, et al. In vitro stimulation of ovarian tumour-associated lymphocytes with a peptide derived from HER2/neu induces cytotoxicity against autologous tumour. Surg Oncol 1995 4 : 41 49.
110. Norell H, et al. Frequent loss of HLA-A2 expression in metastasizing ovarian carcinomas associated with genomic haplotype loss and HLA-A2-restricted HER-2/neu-specific immunity. Cancer Res 2006 66 : 6387 6394.
111. Disis M, Grabstein K, Sleath P, Cheever M. Generation of immunity to the HER-2/neu oncogenic protein in patients with breast and ovarian cancer using a peptide based vaccine. Clin Cancer Res 1999 5 : 1289 1297.
112. Disis ML, et al. Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J Clin Oncol 2002 20 : 2624 2632.
113. Knutson KL, Schiffman K, Cheever MA, Disis ML. Immunization of cancer patients with a HER-2/neu, HLA-A2 peptide, p369-377, results in short-lived peptide-specific immunity. Clin Cancer Res 2002 8 : 1014 1018.
114. Lambeck A, et al. P53-specific T cell responses in patients with malignant and benign ovarian tumors: implications for p53 based immunotherapy. Int J Cancer 2007 121 : 606 614.
115. Snijdewint FG, et al. Cellular and humoral immune responses to MUC1 mucin and tandem-repeat peptides in ovarian cancer patients and controls. Cancer Immunol Immunother 1999 48 : 47 55.
116. Peoples GE, Anderson BW, Fisk B, Kudelka AP, Wharton JT, Ioannides CG. Ovarian cancer-associated lymphocyte recognition of folate binding protein peptides. Ann Surg Oncol 1998 5 : 743 750.
117. Peoples GE, et al. Vaccine implications of folate binding protein, a novel cytotoxic T lymphocyte-recognized antigen system in epithelial cancers. Clin Cancer Res 1999 5 : 4214 4223.
118. Knutson KL, et al. T-cell immunity to the folate receptor alpha is prevalent in women with breast or ovarian cancer. J Clin Oncol 2006 24 : 4254 4261.
119. *0401/0402 patients with epithelial ovarian cancer. Cancer Immun 2004 4 : 12.
120. Valmori D, et al. Expression of synovial sarcoma X (SSX) antigens in epithelial ovarian cancer and identification of SSX-4 epitopes recognized by CD4+ T cells. Clin Cancer Res 2006 12 : 398 404.
121. Yoshino I, Goedegebuure PS, Peoples GE, Lee KY, Eberlein TJ. Human tumor-infiltrating CD4+ T cells react to B cell lines expressing heat shock protein 70. J Immunol 1994 153 : 4149 4158.
122. Schultes BC, Whiteside TL. Monitoring of immune responses to CA125 with an IFN-gamma ELISPOT assay. J Immunol Methods 2003 279 : 1 15.
123. Ishiyama S, et al. Novel natural immunogenic peptides from Numb1 and Notch1 proteins for CD8+ cells in ovarian ascites. Int J Oncol 2007 30 : 889 898.
124. Philip R, et al. Shared immunoproteome for ovarian cancer diagnostics and immunotherapy: potential theranostic approach to cancer. J Proteome Res 2007 6 : 2509 2517.
125. Ramakrishna V, et al. Naturally occurring peptides associated with HLA-A2 in ovarian cancer cell lines identified by mass spectrometry are targets of HLA-A2-restricted cytotoxic T cells. Int Immunol 2003 15 : 751 763.
126. Li G, et al. Human ovarian tumour-derived chaperone-rich cell lysate (CRCL) elicits T cell responses in vitro. Clin Exp Immunol 2007 148 : 136 145.
127. Kooi S, Zhang HZ, Patenia R, Edwards CL, Platsoucas CD, Freedman RS. HLA class I expression on human ovarian carcinoma cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro in low concentrations of recombinant interleukin-2. Cell Immunol 1996 174 : 116 128.
128. Puiffe ML, et al. Characterization of ovarian cancer ascites on cell invasion, proliferation, spheroid formation, and gene expression in an in vitro model of epithelial ovarian cancer. Neoplasia 2007 9 : 820 829.
129. Mustea A, et al. Expression of IL-10 in patients with ovarian carcinoma. Anticancer Res 2006 26 : 1715 1718.
130. Santin AD, et al. Increased levels of interleukin-10 and transforming growth factor-beta in the plasma and ascitic fluid of patients with advanced ovarian cancer. BJOG 2001 108 : 804 808.
131. Pisa P, et al. Selective expression of interleukin 10, interferon gamma, and granulocyte-macrophage colony-stimulating factor in ovarian cancer biopsies. Proc Natl Acad Sci USA 1992 89 : 7708 7712.
132. Merogi AJ, Marrogi AJ, Ramesh R, Robinson WR, Fermin CD, Freeman SM. Tumor-host interaction: analysis of cytokines, growth factors, and tumor-infiltrating lymphocytes in ovarian carcinomas. Hum Pathol 1997 28 : 321 331.
133. Minas V, et al. Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation. Br J Cancer 2007 97 : 637 645.
134. Mezzanzanica D, et al. CD95-mediated apoptosis is impaired at receptor level by cellular FLICE-inhibitory protein (long form) in wild-type p53 human ovarian carcinoma. Clin Cancer Res 2004 10 : 5202 5214.
135. Abrahams VM, et al. Epithelial ovarian cancer cells secrete functional Fas ligand. Cancer Res 2003 63 : 5573 5581.
136. Rabinowich H, Reichert TE, Kashii Y, Gastman BR, Bell MC, Whiteside TL. Lymphocyte apoptosis induced by Fas ligand- expressing ovarian carcinoma cells. Implications for altered expression of T cell receptor in tumor-associated lymphocytes. J Clin Invest 1998 101 : 2579 2588.
137. Taylor DD, Gercel-Taylor C, Lyons KS, Stanson J, Whiteside TL. T-cell apoptosis and suppression of T-cell receptor/CD3-zeta by Fas ligand-containing membrane vesicles shed from ovarian tumors. Clin Cancer Res 2003 9 : 5113 5119.
138. Baldwin RL, Tran H, Karlan BY. Primary ovarian cancer cultures are resistant to Fas-mediated apoptosis. Gynecol Oncol 1999 74 : 265 271.
139. Ghahremani M, Foghi A, Dorrington JH. Activation of Fas ligand/receptor system kills ovarian cancer cell lines by an apoptotic mechanism. Gynecol Oncol 1998 70 : 275 281.
140. Meinhold-Heerlein I, et al. Expression and potential role of Fas-associated phosphatase-1 in ovarian cancer. Am J Pathol 2001 158 : 1335 1344.
141. Hassan MI, Kassim SK, Saeda L, Laban M, Khalifa A. Ovarian cancer-induced immunosuppression: relationship to tumor necrosis factor-alpha (TNF-alpha) release from ovarian tissue. Anticancer Res 1999 19 : 5657 5662.
142. Simonitsch I, Krupitza G. Autocrine self-elimination of cultured ovarian cancer cells by tumour necrosis factor alpha (TNF-alpha). Br J Cancer 1998 78 : 862 870.
143. Gordinier ME, et al. Quantitative analysis of transforming growth factor beta 1 and 2 in ovarian carcinoma. Clin Cancer Res 1999 5 : 2498 2505.
144. Li X, Ye F, Chen H, Lu W, Wan X, Xie X. Human ovarian carcinoma cells generate CD4(+)CD25(+) regulatory T cells from peripheral CD4(+)CD25(-) T cells through secreting TGF-beta. Cancer Lett 2007 253 : 144 153.
145. Mesiano S, Ferrara N, Jaffe RB. Role of vascular endothelial growth factor in ovarian cancer: inhibition of ascites formation by immunoneutralization. Am J Pathol 1998 153 : 1249 1256.
146. Hsieh CY, et al. Overexpression of Her-2/NEU in epithelial ovarian carcinoma induces vascular endothelial growth factor C by activating NF-kappa B: implications for malignant ascites formation and tumor lymphangiogenesis. J Biomed Sci 2004 11 : 249 259.
147. Dong H, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002 8 : 793 800.
148. Choi IH, et al. Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol 2003 171 : 4650 4654.
149. Tringler B, et al. B7-H4 overexpression in ovarian tumors. Gynecol Oncol 2006 100 : 44 52.
150. Salceda S, et al. The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation. Exp Cell Res 2005 306 : 128 141.
151. Zou W, et al. Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med 2001 7 : 1339 1346.
152. Nakashima M, Sonoda K, Watanabe T. Inhibition of cell growth and induction of apoptotic cell death by the human tumor-associated antigen RCAS1. Nat Med 1999 5 : 938 942.
153. Suzuki T, et al. EBAG9/RCAS1 in human breast carcinoma: a possible factor in endocrine-immune interactions. Br J Cancer 2001 85 : 1731 1737.
154. Sonoda K, et al. Clinical significance of RCAS1 as a biomarker of ovarian cancer. Oncol Rep 2007 17 : 623 628.
155. de Bruijn HW, ten Hoor KA, van der Zee AG. Serum and cystic fluid levels of soluble interleukin-2 receptor-alpha in patients with epithelial ovarian tumors are correlated. Tumour Biol 1998 19 : 160 166.
156. Elg SA, Hill RB, Heldman L, Ramakrishnan S. The in vitro effect on T cell function of soluble IL-2Ralpha from advanced ovarian cancer ascites. Gynecol Oncol 1997 66 : 133 137.
157. Maccio A, Lai P, Santona MC, Pagliara L, Melis GB, Mantovani G. High serum levels of soluble IL-2 receptor, cytokines, and C reactive protein correlate with impairment of T cell response in patients with advanced epithelial ovarian cancer. Gynecol Oncol 1998 69 : 248 252.
158. Negus RP, Stamp GW, Hadley J, Balkwill FR. Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am J Pathol 1997 150 : 1723 1734.
159. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 2004 4 : 71 78.
160. Sica A, et al. Defective expression of the monocyte chemotactic protein-1 receptor CCR2 in macrophages associated with human ovarian carcinoma. J Immunol 2000 164 : 733 738.
161. Gordon IO, Freedman RS. Defective antitumor function of monocyte-derived macrophages from epithelial ovarian cancer patients. Clin Cancer Res 2006 12 : 1515 1524.
162. Duluc D, et al. Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated-macrophage-like cells. Blood 2007 110 : 4319 4330.
163. Hagemann T, et al. Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J Immunol 2006 176 : 5023 5032.
164. Loercher AE, Nash MA, Kavanagh JJ, Platsoucas CD, Freedman RS. Identification of an IL-10-producing HLA-DR-negative monocyte subset in the malignant ascites of patients with ovarian carcinoma that inhibits cytokine protein expression and proliferation of autologous T cells. J Immunol 1999 163 : 6251 62560.
165. Helal Tel A, Alla AE, Laban MA, Fahmy RM. Immunophenotyping of tumor-infiltrating mononuclear cells in ovarian carcinoma. Pathol Oncol Res 2004 10 : 80 84.
166. Lambeck AJ, et al. Serum cytokine profiling as a diagnostic and prognostic tool in ovarian cancer: a potential role for interleukin 7. Clin Cancer Res 2007 13 : 2385 2391.
167. Xie X, Ye D, Chen H, Lu W, Cheng B, Zhong H. Interleukin-7 and suppression of local peritoneal immunity in ovarian carcinoma. Int J Gynaecol Obstet 2004 85 : 151 158.
168. Ripley D, Shoup B, Majewski A, Chegini N. Differential expression of interleukins IL-13 and IL-15 in normal ovarian tissue and ovarian carcinomas. Gynecol Oncol 2004 92 : 761 768.
169. Hakkarainen T, et al. CD40 is expressed on ovarian cancer cells and can be utilized for targeting adenoviruses. Clin Cancer Res 2003 9 : 619 624.
170. Melichar B, Patenia R, Gallardo S, Melicharova K, Hu W, Freedman RS. Expression of CD40 and growth-inhibitory activity of CD40 ligand in ovarian cancer cell lines. Gynecol Oncol 2007 104 : 707 713.
171. Conejo-Garcia JR, et al. Ovarian carcinoma expresses the NKG2D ligand Letal and promotes the survival and expansion of CD28- antitumor T cells. Cancer Res 2004 64 : 2175 2182.
172. Roby KF, et al. Development of a syngeneic mouse model for events related to ovarian cancer. Carcinogenesis 2000 21 : 585 591.
173. Yang T, Wall EM, Milne K, Theiss P, Watson P, Nelson BH. CD8+ T Cells Induce Complete Regression of Advanced Ovarian Cancers by an Interleukin (IL)-2/IL-15 Dependent Mechanism. Clin Cancer Res 2007 13 : 7172 7180.
174. Obeid M, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 2007 13 : 54 61.
175. Obeid M, et al. Leveraging the immune system during chemotherapy: moving calreticulin to the cell surface converts apoptotic death from "silent" to immunogenic. Cancer Res 2007 67 : 7941 7944.
176. Apetoh L, et al. The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy. Immunol Rev 2007 220 : 47 59.
177. Dong Xda E, et al. 1997. High mobility group box I (HMGB1) release from tumor cells after treatment: implications for development of targeted chemoimmunotherapy. J Immunother 2007 30 : 596 606.
178. Machiels JP, 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 Res 2001 61 : 3689 3697.
179. van Lunzen J, et al. Transfer of autologous gene-modified T cells in HIV-infected patients with advanced immunodeficiency and drug-resistant virus. Mol Ther 2007 15 : 1024 1033.
180. Bae SH, Park YJ, Park JB, Choi YS, Kim MS, Sin JI. Therapeutic synergy of human papillomavirus E7 subunit vaccines plus cisplatin in an animal tumor model: causal involvement of increased sensitivity of cisplatin-treated tumors to CTL-mediated killing in therapeutic synergy. Clin Cancer Res 2007 13 : 341 349.
181. Kotsakis A, et al. Docetaxel-induced lymphopenia in patients with solid tumors: a prospective phenotypic analysis. Cancer 2000 89 : 1380 1386.
182. Tong AW, et al. Cellular immune profile of patients with advanced cancer before and after taxane treatment. Am J Clin Oncol 2000 23 : 463 472.
183. Melichar B, Touskova M, Dvorak J, Jandik P, Kopecky O. The peripheral blood leukocyte phenotype in patients with breast cancer: effect of doxorubicin/paclitaxel combination chemotherapy. Immunopharmacol Immunotoxicol 2001 23 : 163 173.
184. Souglakos J, et al. Nonneutropenic febrile episodes associated with docetaxel-based chemotherapy in patients with solid tumors. Cancer 2002 95 : 1326 1333.
185. Tsavaris N, Kosmas C, Vadiaka M, Kanelopoulos P, Boulamatsis D. Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes. Br J Cancer 2002 87 : 21 27.
186. Carson WE III., Shapiro CL, Crespin TR, Thornton LM, Andersen BL Cellular immunity in breast cancer patients completing taxane treatment. Clin Cancer Res 2004 10 : 3401 3409.
187. Chan OT, Yang LX. The immunological effects of taxanes. Cancer Immunol Immunother 2000 49 : 181 185.
188. Fitzpatrick FA, Wheeler R. The immunopharmacology of paclitaxel (Taxol), docetaxel (Taxotere), and related agents. Int Immunopharmacol 2003 3 : 1699 1714.
189. Demaria S, et al. Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy. Clin Cancer Res 2001 7 : 3025 3030.
190. Tsuda N, et al. Taxol increases the amount and T cell activating ability of self-immune stimulatory multimolecular complexes found in ovarian cancer cells. Cancer Res 2007 67 : 8378 8387.
191. Shea TC. Mobilization of peripheral blood progenitor cells with paclitaxel-based chemotherapy. Semin Oncol 1997 24 (Suppl.) : S2-105 S2-107.
192. Riesbeck K. Cisplatin at clinically relevant concentrations enhances interleukin-2 synthesis by human primary blood lymphocytes. Anticancer Drugs 1999 10 : 219 227.
193. Tsuda H, Kitahashi S, Umesaki N, Kanaoka Y, Kawabata M, Ogita S. Abrogation of suppressor cells activity by cis-diamminedichloroplatinum (CDDP) treatment using therapeutic doses in ovarian cancer patients. Gynecol Oncol 1994 52 : 218 221.
194. Bagnoli M, et al. Sensitization of p53-mutated epithelial ovarian cancer to CD95-mediated apoptosis is synergistically induced by cisplatin pretreatment. Mol Cancer Ther 2007 6 : 762 772.
195. Coleman S, Clayton A, Mason MD, Jasani B, Adams M, Tabi Z. Recovery of CD8+ T-cell function during systemic chemotherapy in advanced ovarian cancer. Cancer Res 2005 65 : 7000 7006.
196. Nesslinger NJ, et al. Standard treatments induce antigen-specific immune responses in prostate cancer. Clin Cancer Res 2007 13 : 1493 1502.
197. Windbichler GH, et al. Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer 2000 82 : 1138 1144.
198. Sabbatini P, Odunsi K. Immunologic approaches to ovarian cancer treatment. J Clin Oncol 2007 25 : 2884 2893.
199. Wei S, et al. Interleukin-2 administration alters the CD4+FOXP3+ T-cell pool and tumor trafficking in patients with ovarian carcinoma. Cancer Res 2007 67 : 7487 7494.
200. Aoki Y, et al. Use of adoptive transfer of tumor-infiltrating lymphocytes alone or in combination with cisplatin-containing chemotherapy in patients with epithelial ovarian cancer. Cancer Res 1991 51 : 1934 1939.
201. Fujita K, et al. Prolonged disease-free period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Clin Cancer Res 1995 1 : 501 507.
202. Freedman RS, et al. Intraperitoneal adoptive immunotherapy of ovarian carcinoma with tumor-infiltrating lymphocytes and low-dose recombinant interleukin-2: a pilot trial. J Immunother Emphasis Tumor Immunol 1994 16 : 198 210.