Immune Therapy for Ovarian Cancer: Promise and Pitfalls

REFERENCES

• Ioannides CG, Fisk B, Pollack MS, Cytotoxic T-cell clones isolated from ovarian tumour infiltrating lymphocytes recognize common determinants on non-ovarian tumour clones. Scand J Immunol 1993;37:413–424.
   Google Scholar
• Peoples GE, Goedegebuure PS, Smith R, Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proc Natl Acad Sci U S A 1995;92:432–436.
   PubMed Web of Science ®Google Scholar
• Wagner U, Schlebusch H, Kohler S, Immunological responses to the tumor-associated antigen CA125 in patients with advanced ovarian cancer induced by the murine monoclonal anti-idiotype vaccine ACA125. Hybridoma 1997;16:33–40.
   PubMedGoogle Scholar
• Disis ML, Gooley TA, Rinn K, 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Qian HN, Liu GZ, Cao SJ, The experimental study of ovarian carcinoma vaccine modified by human B7–1 and IFN-gamma genes. Int J Gynecol Cancer 2002;12:80–85.
   PubMed Web of Science ®Google Scholar
• Curiel TJ, Wei S, Dong H, Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 2003;9:562–567.
   PubMed Web of Science ®Google Scholar
• Curiel TJ, Coukos G, Zou L, Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004;10:942–949.
   PubMed Web of Science ®Google Scholar
• Vlad AM, Kettel JC, Alajez NM, MUC1 immunobiology: from discovery to clinical applications. Adv Immunol 2004;82:249–293.
   PubMed Web of Science ®Google Scholar
• Diefenbach CS, Gnjatic S, Sabbatini P, Safety and immunogenicity study of NY-ESO-1b peptide and montanide ISA-51 vaccination of patients with epithelial ovarian cancer in high-risk first remission. Clin Cancer Res 2008;14:2740–2748.
   PubMedGoogle Scholar
• Coliva A, Zacchetti A, Luison E, 90Y Labeling of monoclonal antibody MOv18 and preclinical validation for radioimmunotherapy of human ovarian carcinomas. Cancer Immunol Immunother 2005;54:1200–1213.
   PubMed Web of Science ®Google Scholar
• Mantovani LT, Miotti S, Menard S, Folate binding protein distribution in normal tissues and biological fluids from ovarian carcinoma patients as detected by the monoclonal antibodies MOv18 and MOv19. Eur J Cancer 1994;30A:363–369.
   PubMed Web of Science ®Google Scholar
• Thor A, Gorstein F, Ohuchi N, Tumor-associated glycoprotein (TAG-72) in ovarian carcinomas defined by monoclonal antibody B72.3. J Natl Cancer Inst 1986;76:995–1006.
   PubMed Web of Science ®Google Scholar
• Chang K, Pastan I. Molecular cloning of mesothelin, a differentiation antigen present on mesothelium, mesotheliomas, and ovarian cancers. Proc Natl Acad Sci U S A 1996;93:136–140.
   PubMed Web of Science ®Google Scholar
• Cheng WF, Huang CY, Chang MC, High mesothelin correlates with chemoresistance and poor survival in epithelial ovarian carcinoma. Br J Cancer 2009;100:1144–1153.
   PubMed Web of Science ®Google Scholar
• Inoue M, Ogawa H, Nakanishi K, Clinical value of sialyl Tn antigen in patients with gynecologic tumors. Obstet Gynecol 1990;75:1032–1036.
   PubMed Web of Science ®Google Scholar
• Sandmaier BM, Oparin DV, Holmberg LA, Evidence of a cellular immune response against sialyl-Tn in breast and ovarian cancer patients after high-dose chemotherapy, stem cell rescue, and immunization with Theratope STn-KLH cancer vaccine. J Immunother 1999;22:54–66.
   PubMed Web of Science ®Google Scholar
• Campbell IG, Freemont, PS, Foulkes W, Trowsdale J. An ovarian tumor marker with homology to vaccinia virus contains an IgV-like region and multiple transmembrane domains. Cancer Res 1992;52:5416–5420.
   PubMed Web of Science ®Google Scholar
• Zhang L, Conejo-Garcia JR, Katsaros D, Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003;348:203–213.
   PubMed Web of Science ®Google Scholar
• Pardoll D. T cells and tumours. Nature 2001;411:1010–1012.
   PubMed Web of Science ®Google Scholar
• Bindea G, Mlecnik B, Fridman WH, Natural immunity to cancer in humans. Curr Opin Immunol 2010;22:215–222.
   PubMed Web of Science ®Google Scholar
• Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol 2004;22:329–360.
   PubMed Web of Science ®Google Scholar
• Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 2006;6:295–307.
   PubMed Web of Science ®Google Scholar
• Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 2006;6:715–727.
   PubMed Web of Science ®Google Scholar
• Sehouli J, Senyuva F, Fotopoulou C, Intra-abdominal tumor dissemination pattern and surgical outcome in 214 patients with primary ovarian cancer. J Surg Oncol 2009;99:424–427.
   PubMed Web of Science ®Google Scholar
• Lamers CH, Bolhuis RL, Warnaar SO, Local but no systemic immunomodulation by intraperitoneal treatment of advanced ovarian cancer with autologous T lymphocytes re-targeted by a bi-specific monoclonal antibody. Int J Cancer 1997;73:211–219.
   PubMed Web of Science ®Google Scholar
• Oei AL, Verheijen RH, Seiden MV, Decreased intraperitoneal disease recurrence in epithelial ovarian cancer patients receiving intraperitoneal consolidation treatment with yttrium-90-labeled murine HMFG1 without improvement in overall survival. Int J Cancer 2007;120:2710–2714.
   PubMed Web of Science ®Google Scholar
• StuartSS GC, Nation JG, Snider DD, Thunberg P. Intraperitoneal interferon in the management of malignant ascites. Cancer 1993;71:2027–2030.
   Google Scholar
• Gerber SA, Rybalko VY, Bigelow CE, (Preferential attachment of peritoneal tumor metastases to omental immune aggregates and possible role of a unique vascular microenvironment in metastatic survival and growth. Am J Pathol 2006;169:1739–1752.
   PubMed Web of Science ®Google Scholar
• Khan SM, Funk HM, Thiolloy S, In vitro metastatic colonization of human ovarian cancer cells to the omentum. Clin Exp Metastasis 2010;27:185–196.
   PubMed Web of Science ®Google Scholar
• Bedford PA, Todorovic V, Westcott ED, Adipose tissue of human omentum is a major source of dendritic cells, which lose MHC Class II and stimulatory function in Crohn's disease. J Leukoc Biol 2006;80:546–554.
   Google Scholar
• Lynch L, O'Shea, D, Winter, DC, Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity. Eur J Immunol 2009;39:1893–1901.
   PubMedGoogle Scholar
• Rangel-Moreno J, Moyron-Quiroz JE, Carragher DM, Omental milky spots develop in the absence of lymphoid tissue-inducer cells and support B and T cell responses to peritoneal antigens. Immunity 2009;30:731–743.
   PubMed Web of Science ®Google Scholar
• Nunez-Cruz S, Guerra M, Connolly D, Ovarian tumor infiltrating lymphocytes B have pro angiogenic properties. Journal of Immunology 2010;184:101–107 (abstract).
   Google Scholar
• Parungo CP, Soybel DI, Colson YL, Lymphatic drainage of the peritoneal space: a pattern dependent on bowel lymphatics. Ann Surg Oncol 2007;14:286–298.
   PubMed Web of Science ®Google Scholar
• Feki A, Berardi P, Bellingan G, Dissemination of intraperitoneal ovarian cancer: Discussion of mechanisms and demonstration of lymphatic spreading in ovarian cancer model. Crit Rev Oncol Hematol 2009;72:1–9.
   PubMed Web of Science ®Google Scholar
• Roby KF, Taylor CC, Sweetwood JP, Development of a syngeneic mouse model for events related to ovarian cancer. Carcinogenesis 2000;21:585–591.
   PubMed Web of Science ®Google Scholar
• Dinulescu DM, Ince TA, Quade BJ, Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer. Nat Med 2005;11:63–70.
   PubMed Web of Science ®Google Scholar
• Xing D, Orsulic S. A mouse model for the molecular characterization of brca1-associated ovarian carcinoma. Cancer Res 2006;66:8949–8953.
   Google Scholar
• Nunez-Cruz S, Connolly DC, Scholler N. An orthotopic model of serous ovarian cancer in immunocompetent mice for in vivo tumor imaging and monitoring of tumor immune responses. J Vis Exp (2011).
   Google Scholar
• Scarlett U.K. Progressive abrogation of early anti-tumor immunity by dendritic cells provides new opportunities for novel diagnostic interventions. Keystone Symposium on Dendritic Cells and Tumor Immunology, Santa Fe, New Mexico, USA abstract J8 342 (2011).
   Google Scholar
• Bast RC, Jr., Feeney M, Lazarus H, Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest 1981;68:1331–1337.
   PubMed Web of Science ®Google Scholar
• Epenetos AA, Britton KE, Mather S, Targeting of iodine-123-labelled tumour-associated monoclonal antibodies to ovarian, breast, and gastrointestinal tumours. Lancet 1982;2:999–1005.
   PubMed Web of Science ®Google Scholar
• Oei AL, Sweep FC, Thomas CM, The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (review). Int J Oncol 2008;32:1145–1157.
   PubMed Web of Science ®Google Scholar
• Epenetos AA, Munro AJ, Stewart S, Antibody-guided irradiation of advanced ovarian cancer with intraperitoneally administered radiolabeled monoclonal antibodies. J Clin Oncol 1987;5:1890–1899.
   PubMed Web of Science ®Google Scholar
• Riva P, Marangolo M, Lazzari S, Locoregional immunotherapy of human ovarian cancer: preliminary results. Int J Rad Appl Instrum B 1989;16:659–666.
   Google Scholar
• Stewart JS, Hird V, Snook D, Intraperitoneal yttrium-90-labeled monoclonal antibody in ovarian cancer. J Clin Oncol 1990;8:1941–1950.
   PubMed Web of Science ®Google Scholar
• Hird V, Maraveyas A, Snook D, Adjuvant therapy of ovarian cancer with radioactive monoclonal antibody. Br J Cancer 1993;68:403–406.
   PubMed Web of Science ®Google Scholar
• Epenetos AA, Hird V, Lambert H, Long term survival of patients with advanced ovarian cancer treated with intraperitoneal radioimmunotherapy. Int J Gynecol Cancer 2000;10:44–46.
   PubMed Web of Science ®Google Scholar
• Gordon AN, Schultes BC, Gallion H, CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients. Gynecol Oncol 2004;94:340–351.
   PubMed Web of Science ®Google Scholar
• Ehlen TG, Hoskins PJ, Miller D, A pilot phase 2 study of oregovomab murine monoclonal antibody to CA125 as an immunotherapeutic agent for recurrent ovarian cancer. Int J Gynecol Cancer 2005;15:1023–1034.
   PubMed Web of Science ®Google Scholar
• Reinartz S, Kohler, S, Schlebusch, H, Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II). Clin Cancer Res 2004;10:1580–1587.
   PubMed Web of Science ®Google Scholar
• Pfisterer J, du Bois A, Sehouli J, The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR. Ann Oncol 2006;17:1568–1577.
   PubMed Web of Science ®Google Scholar
• Pfisterer J, Harter P, Simonelli C, Abagovomab for ovarian cancer. Expert Opin Biol Ther 2011;11:395–403.
   PubMed Web of Science ®Google Scholar
• Curnow RT. Clinical experience with CD64-directed immunotherapy. An overview. Cancer Immunol Immunother 1997;45:210–215.
   PubMed Web of Science ®Google Scholar
• Leffers N, Daemen T, Helfrich W, Antigen-specific active immunotherapy for ovarian cancer. Cochrane Database Syst Rev, CD007287 (2010).
   Google Scholar
• Pestka S, Krause CD, Walter MR. Interferons, interferon-like cytokines, and their receptors. Immunol Rev 2004;202:8–32.
   PubMed Web of Science ®Google Scholar
• Kirkwood J. Cancer immunotherapy: the interferon-alpha experience. Semin Oncol 2002;29:18–26.
   PubMed Web of Science ®Google Scholar
• Berek JS, Hacker, NF, Lichtenstein, A, Intraperitoneal recombinant alpha-interferon for “salvage” immunotherapy in stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. Cancer Res 1985;45:4447–4453.
   PubMed Web of Science ®Google Scholar
• Bezwoda WR, Seymour L, Dansey R. Intraperitoneal recombinant interferon-alpha 2b for recurrent malignant ascites due to ovarian cancer. Cancer 1989;64:1029–1033.
   Google Scholar
• Nardi M, Cognetti F, Pollera CF, Intraperitoneal recombinant alpha-2-interferon alternating with cisplatin as salvage therapy for minimal residual-disease ovarian cancer: a phase II study. J Clin Oncol 1990;8:1036–1041.
   PubMed Web of Science ®Google Scholar
• Tedjarati S, Baker CH, Apte S, Synergistic therapy of human ovarian carcinoma implanted orthotopically in nude mice by optimal biological dose of pegylated interferon alpha combined with paclitaxel. Clin Cancer Res 2002;8:2413–2422.
   PubMed Web of Science ®Google Scholar
• Metcalf KS, Selby PJ, Trejdosiewicz LK, Southgate J. Culture of ascitic ovarian cancer cells as a clinically-relevant ex vivo model for the assessment of biological therapies. Eur J Gynaecol Oncol 1998;19:113–119.
   Google Scholar
• Thibodeaux SR, Curiel TJ. Treatment of ovarian cancer with interferon-alpha plus Treg depletion. Fourth World Immune Regulation Meeting Davos, SZ (2010).
   Google Scholar
• Sterman DH, Recio A, Haas AR, A phase I trial of repeated intrapleural adenoviral-mediated interferon-beta gene transfer for mesothelioma and metastatic pleural effusions. Mol Ther 2010;18:852–860.
   PubMed Web of Science ®Google Scholar
• Moserle L, Indraccolo S, Ghisi M, The side population of ovarian cancer cells is a primary target of IFN-alpha antitumor effects. Cancer Res 2008;68:5658–5668.
   PubMed Web of Science ®Google Scholar
• Chen JT, Hasumi K, Masubuchi K. Interferon-alpha, interferon-gamma and sizofiran in the adjuvant therapy in ovarian cancer–a preliminary trial. Biotherapy 1992;5:275–280.
   Google Scholar
• Pujade-Lauraine E, Guastalla JP, Colombo N, Intraperitoneal recombinant interferon gamma in ovarian cancer patients with residual disease at second-look laparotomy. J Clin Oncol 1996;14:343–350.
   PubMed Web of Science ®Google Scholar
• Windbichler GH, Hausmaninger H, Stummvoll W, Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer 2000;82:1138–1144.
   PubMed Web of Science ®Google Scholar
• Freedman RS, Kudelka AP, Kavanagh JJ, Clinical and biological effects of intraperitoneal injections of recombinant interferon-gamma and recombinant interleukin 2 with or without tumor-infiltrating lymphocytes in patients with ovarian or peritoneal carcinoma. Clin Cancer Res 2000;6:2268–2278.
   PubMed Web of Science ®Google Scholar
• Marth C, Muller-Holzner E, Greiter E, Gamma-interferon reduces expression of the protooncogene c-erbB-2 in human ovarian carcinoma cells. Cancer Res 1990;50:7037–7041.
   PubMed Web of Science ®Google Scholar
• Madiyalakan R, Yang R, Schultes BC, OVAREX MAb-B43.13:IFN-gamma could improve the ovarian tumor cell sensitivity to CA125-specific allogenic cytotoxic T cells. Hybridoma 1997;16:41–45.
   Google Scholar
• Burke F, East N, Upton C, Interferon gamma induces cell cycle arrest and apoptosis in a model of ovarian cancer: enhancement of effect by batimastat. Eur J Cancer 1997;33:1114–1121.
   PubMedGoogle Scholar
• Antony GK, Dudek AZ. Interleukin 2 in cancer therapy. Curr Med Chem 2010;17:3297–3302.
   PubMed Web of Science ®Google Scholar
• Recchia F, Di Orio F, Candeloro G, Maintenance immunotherapy in recurrent ovarian cancer: long term follow-up of a phase II study. Gynecol Oncol 2010;116:202–207.
   PubMed Web of Science ®Google Scholar
• Vlad AM, Budiu RA, Lenzner DE, A phase II trial of intraperitoneal interleukin-2 in patients with platinum-resistant or platinum-refractory ovarian cancer. Cancer Immunol Immunother (2009).
   Google Scholar
• Perillo A, Pierelli L, Battaglia A, Administration of low-dose interleukin-2 plus G-CSF/EPO early after autologous PBSC transplantation: effects on immune recovery and NK activity in a prospective study in women with breast and ovarian cancer. Bone Marrow Transplant 2002;30:571–578.
   Google Scholar
• Wei S, Kryczek I, Edwards RP, Interleukin-2 administration alters the CD4+FOXP3+ T-cell pool and tumor trafficking in patients with ovarian carcinoma. Cancer Res 2007;67:7487–7494.
   PubMed Web of Science ®Google Scholar
• Han X, Wilbanks GD, Devaja O, IL-2 Enhances Standard IFNgamma/LPS Activation of Macrophage Cytotoxicity to Human Ovarian Carcinoma in Vitro: A Potential for Adoptive Cellular Immunotherapy. Gynecol Oncol 1999;75:198–210.
   PubMed Web of Science ®Google Scholar
• Apte SM, Vadhan-Raj S, Cohen L, Cytokines, GM-CSF and IFNgamma administered by priming and post-chemotherapy cycling in recurrent ovarian cancer patients receiving carboplatin. J Transl Med 2006;4:16.
   Google Scholar
• Disis ML, Grabstein KH, Sleath PR, Cheever MA. 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.
   PubMed Web of Science ®Google Scholar
• Disis M.L., Rinn K, Knutson KL, Flt3 ligand as a vaccine adjuvant in association with HER-2/neu peptide-based vaccines in patients with HER-2/neu-overexpressing cancers. Blood 2002;99:2845–2850.
   PubMed Web of Science ®Google Scholar
• Zhou G, Drake CG, Levitsky HI. Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood 2006;107:628–636.
   PubMed Web of Science ®Google Scholar
• Canevari S, Stoter G, Arienti F, Regression of advanced ovarian carcinoma by intraperitoneal treatment with autologous T lymphocytes retargeted by a bispecific monoclonal antibody. J Natl Cancer Inst 1995;87:1463–1469.
   PubMed Web of Science ®Google Scholar
• Freedman RS, Platsoucas CD. Immunotherapy for peritoneal ovarian carcinoma metastasis using ex vivo expanded tumor infiltrating lymphocytes. Cancer Treat Res 1996;82:115–146.
   PubMedGoogle Scholar
• Gritzapis AD, Sotiriadou NN, Papamichail M, Baxevanis CN. Generation of human tumor-specific CTLs in HLA-A2.1-transgenic mice using unfractionated peptides from eluates of human primary breast and ovarian tumors. Cancer Immunol Immunother 2004;53:1027–1040.
   Google Scholar
• Lum LG, LeFever AV, Treisman JS, Immune modulation in cancer patients after adoptive transfer of anti-CD3/anti-CD28-costimulated T cells-phase I clinical trial. J Immunother 2001;24:408–419.
   Web of Science ®Google Scholar
• Kershaw MH, Westwood JA, Parker LL, A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 2006;12:6106–6115.
   PubMed Web of Science ®Google Scholar
• Chekmasova AA, Brentjens RJ. Adoptive T cell immunotherapy strategies for the treatment of patients with ovarian cancer. Discov Med 2010;9:62–70.
   PubMedGoogle Scholar
• Lee JM, Yoon SH, Kim HS, Direct and indirect antitumor effects by human peripheral blood lymphocytes expressing both chimeric immune receptor and interleukin-2 in ovarian cancer xenograft model. Cancer Gene Ther 2010;17:742–750.
   Google Scholar
• Nesbeth YC, Martinez DG, Toraya S, CD4+ T cells elicit host immune responses to MHC class II-negative ovarian cancer through CCL5 secretion and CD40-mediated licensing of dendritic cells. J Immunol 2010;184:5654–5662.
   PubMedGoogle Scholar
• Brossart P, Wirths S, Stuhler G, Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood 2000;96:3102–3108.
   PubMed Web of Science ®Google Scholar
• Berd D, Kairys J, Dunton C, Autologous, hapten-modified vaccine as a treatment for human cancers. Semin Oncol 1998;25:646–653.
   PubMed Web of Science ®Google Scholar
• Palucka AK, Ueno H, Fay JW, Banchereau J. Taming cancer by inducing immunity via dendritic cells. Immunol Rev 2007;220:129–150.
   PubMed Web of Science ®Google Scholar
• Hernando JJ, Park TW, Kubler K, Vaccination with autologous tumour antigen-pulsed dendritic cells in advanced gynaecological malignancies: clinical and immunological evaluation of a phase I trial. Cancer Immunol Immunother 2002;51:45–52.
   PubMed Web of Science ®Google Scholar
• Chang CL, Tsai, YC, He, L, Cancer immunotherapy using irradiated tumor cells secreting heat shock protein 70. Cancer Res 2007;67:10047–10057.
   PubMed Web of Science ®Google Scholar
• Gong J, Nikrui N, Chen D, Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol 2000;165:1705–1711.
   PubMed Web of Science ®Google Scholar
• Geller MA, Cooley S, Judson PL, A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. Cytotherapy 2011;13:98–107.
   PubMed Web of Science ®Google Scholar
• Lopez M, Fechtenbaum J, David B, Adoptive immunotherapy with activated macrophages grown in vitro from blood monocytes in cancer patients: a pilot study. J Immunother (1991) 1992;11:209–217.
   PubMed Web of Science ®Google Scholar
• Woo EY, Chu, CS, Goletz, TJ, 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.
   PubMed Web of Science ®Google Scholar
• Sato E, Olson SH, Ahn J, 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 U S A 2005;102:18538–18543.
   PubMed Web of Science ®Google Scholar
• Curiel TJ. Regulatory T cells and treatment of cancer. Curr Opin Immunol 2008;20:241–246.
   PubMed Web of Science ®Google Scholar
• Barnett B, Kryczek I, Cheng P, Regulatory T cells in ovarian cancer: biology and therapeutic potential. Am J Reprod Immunol 2005;54:369–377.
   PubMed Web of Science ®Google Scholar
• Barnett, B., W, Z., Chen P, Curiel TJ. Depleting CD4+CD25+ Regulatory T Cells Improves Immunity in Cancer-Bearing Patients. abstract # LB-311, American Association of Cancer Research Annual Meeting, April 2004, Orlando, FL. (2004).
   Google Scholar
• Coukos G. CCR10 +regulatory T cells are recruited by hypoxic tumor cells via the CCL28 chemokine to promote immune tolerance and angiogenesis in cancer. Keystone Symposium on Dendritic Cells and Tumor Immunology, Santa Fe, New Mexico, USA abstract J8 138 (2011).
   Google Scholar
• Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 2008;8:467–477.
   PubMed Web of Science ®Google Scholar
• Dong H, Strome, SE, Salomao, DR, Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat Med 2002;8:793–800.
   PubMed Web of Science ®Google Scholar
• Lin PY, Sun, L, Thibodeaux, SR, B7-H1-Dependent Sex-Related Differences in Tumor Immunity and Immunotherapy Responses. J Immunol 2010;185:2747–2753.
   PubMed Web of Science ®Google Scholar
• Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev 2008;224:166–182.
   PubMed Web of Science ®Google Scholar
• Egen JG, Kuhns, MS & Allison, JP CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol 2002;3:611–618.
   PubMed Web of Science ®Google Scholar
• Hodi FS, Butler M, Oble DA, Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A 2008;105:3005–3010.
   PubMed Web of Science ®Google Scholar
• Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009;9:162–174.
   PubMed Web of Science ®Google Scholar
• Tomihara K, Guo M, Shin T, Antigen-specific immunity and cross-priming by epithelial ovarian carcinoma-induced CD11b(+)Gr-1(+) cells. J Immunol 2010;184:6151–6160.
   PubMed Web of Science ®Google Scholar
• Yang R, Cai Z, Zhang Y, CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b+ myeloid cells. Cancer Res 2006;66:6807–6815.
   PubMed Web of Science ®Google Scholar
• Jin D, Fan J, Wang L, CD73 on tumor cells impairs antitumor T-cell responses: a novel mechanism of tumor-induced immune suppression. Cancer Res 70:2245–2255.
   Google Scholar
• Sutmuller RP, Morgan ME, Netea MG, Toll-like receptors on regulatory T cells: expanding immune regulation. Trends Immunol 2006;27:387–393.
   PubMed Web of Science ®Google Scholar
• Geller MA, Cooley S, Argenta PA, Toll-like receptor-7 agonist administered subcutaneously in a prolonged dosing schedule in heavily pretreated recurrent breast, ovarian, and cervix cancers. Cancer Immunol Immunother 2010;59:1877–1884.
   PubMed Web of Science ®Google Scholar
• Chao MP, Jaiswal, S, Weissman-Tsukamoto, R, Calreticulin is the dominant pro-phagocytic signal on multiple human cancers and is counterbalanced by CD47. Sci Transl Med 2, 63ra94.
   Google Scholar
• Willingham S. Efficacy of anti-CD47 antibody therapy for human solid tumors. Keystone Symposium on Dendritic Cells and Tumor Immunology, Santa Fe, New Mexico, USA abstract J8 335 (2011).
   Google Scholar
• Zhang YQ, Tsai YC, Monie A, Enhancing the therapeutic effect against ovarian cancer through a combination of viral oncolysis and antigen-specific immunotherapy. Mol Ther 2010;18:692–699.
   PubMed Web of Science ®Google Scholar
• Chen L, Park SM, Tumanov AV, CD95 promotes tumour growth. Nature 2010;465:492–496.
   PubMed Web of Science ®Google Scholar
• Bellati F, Napoletano C, Ruscito I, Complete remission of ovarian cancer induced intractable malignant ascites with intraperitoneal bevacizumab. Immunological observations and a literature review. Invest New Drugs 2010;28:887–894.
   PubMed Web of Science ®Google Scholar
• Kandalaft LE, Singh N, Liao JB, The emergence of immunomodulation: combinatorial immunochemotherapy opportunities for the next decade. Gynecol Oncol 2010;116:222–233.
   PubMed Web of Science ®Google Scholar
• Demaria S, Volm MD, Shapiro RL, Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy. Clin Cancer Res 2001;7:3025–3030.
   PubMed Web of Science ®Google Scholar
• Hales RK, Banchereau J, Ribas A, Assessing oncologic benefit in clinical trials of immunotherapy agents. Ann Oncol 2010;21:1944–1951.
   PubMed Web of Science ®Google Scholar
• Litzinger MT, Fernando R, Curiel TJ, IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity. Blood 2007;110:3192–3201.
   PubMed Web of Science ®Google Scholar