Tumor infiltrating lymphocytes in ovarian cancer

Cancer Biology and Therapy

Volumn 16, Issue 6, 2015, Pages 807-820

  Santoiemma, Phillip P ^a   Powell, Daniel J ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Immunosuppression; Immunotherapy; Ovarian cancer; Prognostic factors; Regulatory T cells; Tumor infiltrating lymphocytes

Indexed keywords

ADOPTIVE IMMUNOTHERAPY; CANCER INHIBITION; CANCER SURVIVAL; CANCER THERAPY; CELL THERAPY; CLINICAL TRIAL (TOPIC); FEMALE; HUMAN; LYMPHOCYTE FUNCTION; META ANALYSIS (TOPIC); NONHUMAN; OVARY CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); REGULATORY T LYMPHOCYTE; REVIEW; TUMOR ASSOCIATED LEUKOCYTE; TUMOR MICROENVIRONMENT; ANIMAL; IMMUNOLOGY; IMMUNOMODULATION; LYMPHOCYTE SUBPOPULATION; METABOLISM; MORTALITY; OVARIAN NEOPLASMS; PATHOLOGY; PROGNOSIS; TREATMENT OUTCOME;

CANCER VACCINE;

ANIMALS; CANCER VACCINES; CLINICAL TRIALS AS TOPIC; FEMALE; HUMANS; IMMUNOMODULATION; IMMUNOTHERAPY, ADOPTIVE; LYMPHOCYTE SUBSETS; LYMPHOCYTES, TUMOR-INFILTRATING; OVARIAN NEOPLASMS; PROGNOSIS; TREATMENT OUTCOME; TUMOR MICROENVIRONMENT;

EID: 84943810799     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.1080/15384047.2015.1040960     Document Type: Review

References (149)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63: 11-30; PMID: 23335087.
2. Chen L, Berek JS. Overview of epithelial carcinoma of the ovary, fallopian tube, and peritoneum. In: Goff B, ed.: UpToDate. Waltham, MA., 2013.
3. Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Pecorelli S, Beller U. Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006; 95 Suppl 1: S161-92; PMID: 17161157; http://dx. doi. org/10. 1016/S0020-7292(06)60033-7.
4. Mann WJ, Chalas EJ, Valea FA. Epithelial ovarian cancer: Initial surgical management. In: Goff B, ed. In: UpToDate. Waltham, MA., 2013.
5. Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, Rubin SC, Kaiser LR, June CH. Regulatory CD4(C)CD25(C) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 2001; 61: 4766-72; PMID: 11406550.
6. Landrum LM, Java J, Mathews CA, Lanneau GS, Jr., Copeland LJ, Armstrong DK, Walker JL. Prognostic factors for stage III epithelial ovarian cancer treated with intraperitoneal chemotherapy: A Gynecologic Oncology Group study. Gynecol Oncol 2013; 130: 12-8; PMID: 23578540; http://dx. doi. org/10. 1016/j. ygyno. 2013. 04. 001.
7. Winter WE, 3rd, Maxwell GL, Tian C, Carlson JW, Ozols RF, Rose PG, Markman M, Armstrong DK, Muggia F, McGuire WP, et al. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2007; 25: 3621-7; PMID: 17704411; http://dx. doi. org/10. 1200/JCO. 2006. 10. 2517.
8. Eggermont A, Robert C, Soria JC, Zitvogel L. Harnessing the immune system to provide longterm survival in patients with melanoma and other solid tumors. Oncoimmunology 2014; 3: e27560.
9. Mittal D, Gubin MM, Schreiber RD, Smyth MJ. New insights into cancer immunoediting and its three component phases-elimination, equilibrium and escape. Curr Opin Immunol 2014; 27C: 16-25; http://dx. doi. org/10. 1016/j. coi. 2014. 01. 004.
10. Dadmarz RD, Ordoubadi A, Mixon A, Thompson CO, Barracchini KC, Hijazi YM, Steller MA, Rosenberg SA, Schwartzentruber DJ. Tumor-infiltrating lymphocytes from human ovarian cancer patients recognize autologous tumor in an MHC class IIrestricted fashion. Cancer J Sci Am 1996; 2: 263-72; PMID: 9166543.
11. Erdag G, Schaefer JT, Smolkin ME, Deacon DH, Shea SM, Dengel LT, Patterson JW, Slingluff CL, Jr. Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma. Cancer research 2012; 72: 1070-80; PMID: 22266112; http://dx. doi. org/10. 1158/0008-5472. CAN-11-3218.
12. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313: 1960-4; PMID: 17008531; http://dx. doi. org/10. 1126/science. 1129139.
13. Ma D, Gu MJ. Immune effect of tumor-infiltrating lymphocytes and its relation to the survival rate of patients with ovarian malignancies. J Tongji Med Univ 1991; 11: 235-9; PMID: 1668016.
14. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003; 348: 203-13; PMID: 12529460; http://dx. doi. org/10. 1056/NEJMoa020177.
15. Raspollini MR, Castiglione F, Rossi Degl'innocenti D, Amunni G, Villanucci A, Garbini F, Baroni G, Taddei GL. Tumour-infiltrating gamma/delta T-lymphocytes are correlated with a brief disease-free interval in advanced ovarian serous carcinoma. Ann Oncol 2005; 16: 590-6; PMID: 15699022; http://dx. doi. org/10. 109/3annonc/mdi112.
16. Tomsova M, Melichar B, Sedlakova I, Steiner I. Prognostic significance of CD3C tumor-infiltrating lymphocytes in ovarian carcinoma. Gynecol Oncol 2008; 108: 415-20; PMID: 18037158; http://dx. doi. org/10. 1016/j. ygyno. 2007. 10. 016.
17. Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, Jungbluth AA, Frosina D, Gnjatic S, Ambrosone C, et al. Intraepithelial CD8C tumor-infiltrating lymphocytes and a high CD8C/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A 2005; 102: 18538-43; PMID: 16344461; http://dx. doi. org/10. 1073/pnas. 0509182102.
18. 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: 40-4; PMID: 12646975; http://dx. doi. org/10. 1272/jnms. 70. 40.
19. Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, Higuchi T, Yagi H, Takakura K, Minato N, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8C T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A 2007; 104: 3360-5; PMID: 17360651; http://dx. doi. org/10. 1073/pnas. 0611533104.
20. Callahan MJ, Nagymanyoki Z, Bonome T, Johnson ME, Litkouhi B, Sullivan EH, Hirsch MS, Matulonis UA, Liu J, Birrer MJ, et al. Increased HLA-DMB expression in the tumor epithelium is associated with increased CTL infiltration and improved prognosis in advanced-stage serous ovarian cancer. Clin Cancer Res 2008; 14: 7667-73; PMID: 19047092; http://dx. doi. org/10. 1158/1078-0432. CCR-08-0479.
21. Adams SF, Levine DA, Cadungog MG, Hammond R, Facciabene A, Olvera N, Rubin SC, Boyd J, Gimotty PA, Coukos G. Intraepithelial T cells and tumor proliferation: impact on the benefit from surgical cytoreduction in advanced serous ovarian cancer. Cancer 2009; 115: 2891-902; PMID: 19472394; http://dx. doi. org/10. 1002/cncr. 24317.
22. Leffers N, Gooden MJ, de Jong RA, Hoogeboom BN, ten Hoor KA, Hollema H, Boezen HM, van der Zee AG, Daemen T, Nijman HW. Prognostic significance of tumor-infiltrating T-lymphocytes in primary and metastatic lesions of advanced stage ovarian cancer. Cancer Immunol Immunother 2009; 58: 449-59; PMID: 18791714; http://dx. doi. org/10. 1007/s00262-008-0583-5.
23. Stumpf M, Hasenburg A, Riener MO, Jutting U, Wang C, Shen Y, Orlowska-Volk M, Fisch P, Wang Z, Gitsch G, et al. Intraepithelial CD8-positive T lymphocytes predict survival for patients with serous stage III ovarian carcinomas: relevance of clonal selection of T lymphocytes. Br J Cancer 2009; 101: 1513-21; PMID: 19861998; http://dx. doi. org/10. 1038/sj. bjc. 6605274.
24. Gooden M, Lampen M, Jordanova ES, Leffers N, Trimbos JB, van der Burg SH, Nijman H, van Hall T. HLA-E expression by gynecological cancers restrains tumor-infiltrating CD8(C) T lymphocytes. Proc Natl Acad Sci U S A 2011; 108: 10656-61; PMID: 21670276; http://dx. doi. org/10. 1073/pnas. 1100354108.
25. Hamanishi J, Mandai M, Abiko K, Matsumura N, Baba T, Yoshioka Y, Kosaka K, Konishi I. The comprehensive assessment of local immune status of ovarian cancer by the clustering of multiple immune factors. Clin Immunol 2011; 141: 338-47; PMID: 21955569; http://dx. doi. org/10. 1016/j. clim. 2011. 08. 013.
26. Vermeij R, de Bock GH, Leffers N, Ten Hoor KA, Schulze U, Hollema H, van der Burg SH, van der Zee AG, Daemen T, Nijman HW. Tumor-infiltrating cytotoxic T lymphocytes as independent prognostic factor in epithelial ovarian cancer with wilms tumor protein 1 overexpression. J Immunother 2011; 34: 516-23; PMID: 21654520; http://dx. doi. org/10. 1097/CJI. 0b013e31821e012f.
27. Milne K, Alexander C, Webb JR, Sun W, Dillon K, Kalloger SE, Gilks CB, Clarke B, Kobel M, Nelson BH. Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes. J Transl Med 2012; 10: 33; PMID: 22369276; http://dx. doi. org/10. 1186/1479-5876-10-33.
28. Nielsen JS, Sahota RA, Milne K, Kost SE, Nesslinger NJ, Watson PH, Nelson BH. CD20C tumor-infiltrating lymphocytes have an atypical CD27-memory phenotype and together with CD8C T cells promote favorable prognosis in ovarian cancer. Clin Cancer Res 2012; 18: 3281-92; PMID: 22553348; http://dx. doi. org/10. 1158/1078-0432. CCR-12-0234.
29. Li K, Mandai M, Hamanishi J, Matsumura N, Suzuki A, Yagi H, Yamaguchi K, Baba T, Fujii S, Konishi I. Clinical significance of the NKG2D ligands, MICA/B and ULBP2 in ovarian cancer: high expression of ULBP2 is an indicator of poor prognosis. Cancer Immunol Immunother 2009; 58: 641-52; PMID: 18791713; http://dx. doi. org/10. 1007/s00262-008-0585-3.
30. Liu M, Matsumura N, Mandai M, Li K, Yagi H, Baba T, Suzuki A, Hamanishi J, Fukuhara K, Konishi I. Classification using hierarchical clustering of tumorinfiltrating immune cells identifies poor prognostic ovarian cancers with high levels of COX expression. Mod Pathol 2009; 22: 373-84; PMID: 18997734; http://dx. doi. org/10. 1038/modpathol. 2008. 187.
31. Barnett JC, Bean SM, Whitaker RS, Kondoh E, Baba T, Fujii S, Marks JR, Dressman HK, Murphy SK, Berchuck A. Ovarian cancer tumor infiltrating T-regulatory (T(reg)) cells are associated with a metastatic phenotype. Gynecol Oncol 2010; 116: 556-62; PMID: 20006900; http://dx. doi. org/10. 1016/j. ygyno. 2009. 11. 020.
32. Han LY, Fletcher MS, Urbauer DL, Mueller P, Landen CN, Kamat AA, Lin YG, Merritt WM, Spannuth WA, Deavers MT, et al. HLA class I antigen processing machinery component expression and intratumoral T-Cell infiltrate as independent prognostic markers in ovarian carcinoma. Clin Cancer Res 2008; 14: 3372-9; PMID: 18519766; http://dx. doi. org/10. 1158/1078-0432. CCR-07-4433.
33. Milne K, Kobel M, Kalloger SE, Barnes RO, Gao D, Gilks CB, Watson PH, Nelson BH. Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PloS one 2009; 4: e6412; PMID: 19641607; http://dx. doi. org/10. 1371/journal. pone. 0006412.
34. Clarke B, Tinker AV, Lee CH, Subramanian S, van de Rijn M, Turbin D, Kalloger S, Han G, Ceballos K, Cadungog MG, et al. Intraepithelial T cells and prognosis in ovarian carcinoma: novel associations with stage, tumor type, and BRCA1 loss. Mod Pathol 2009; 22: 393-402; PMID: 19060844; http://dx. doi. org/10. 1038/modpathol. 2008. 191.
35. Tsiatas ML, Gyftaki R, Liacos C, Politi E, Rodolakis A, Dimopoulos MA, Bamias A. Study of T lymphocytes infiltrating peritoneal metastases in advanced ovarian cancer: associations with vascular endothelial growth factor levels and prognosis in patients receiving platinum-based chemotherapy. Int J Gynecol Cancer 2009; 19: 1329-34; PMID: 20009885; http://dx. doi. org/10. 1111/IGC. 0b013e3181b7a40e.
36. Le Page C, Marineau A, Bonza PK, Rahimi K, Cyr L, Labouba I, Madore J, Delvoye N, Mes-Masson AM, Provencher DM, et al. BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis. PloS One 2012; 7: e38541; PMID: 22685580; http://dx. doi. org/10. 1371/journal. pone. 0038541.
37. Nesbeth YC, Martinez DG, Toraya S, Scarlett UK, Cubillos-Ruiz JR, Rutkowski MR, Conejo-Garcia JR. CD4C 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: 5654-62; http://dx. doi. org/10. 4049/jimmunol. 0903247.
38. Shah CA, Allison KH, Garcia RL, Gray HJ, Goff BA, Swisher EM. Intratumoral T cells, tumor-associated macrophages, and regulatory T cells: association with p53 mutations, circulating tumor DNA and survival in women with ovarian cancer. Gynecol Oncol 2008; 109: 215-9; PMID: 18314181; http://dx. doi. org/10. 1016/j. ygyno. 2008. 01. 010.
39. Al-Attar A, Shehata M, Durrant L, Moseley P, Deen S, Chan S. T cell density and location can influence the prognosis of ovarian cancer. Pathol Oncol Res 2010; 16: 361-70; PMID: 20024633; http://dx. doi. org/10. 1007/s12253-009-9230-5.
40. Dong HP, Elstrand MB, Holth A, Silins I, Berner A, Trope CG, Davidson B, Risberg B. NK-and B-cell infiltration correlates with worse outcome in metastatic ovarian carcinoma. Am J Clin Pathol 2006; 125: 451-8; PMID: 16613351; http://dx. doi. org/10. 1309/15B66DQMFYYM78CJ.
41. Hwang WT, Adams SF, Tahirovic E, Hagemann IS, Coukos G. Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol 2012; 124: 192-8; PMID: 22040834; http://dx. doi. org/10. 1016/j. ygyno. 2011. 09. 039.
42. Sehouli J, Loddenkemper C, Cornu T, Schwachula T, Hoffmuller U, Grutzkau A, Lohneis P, Dickhaus T, Grone J, Kruschewski M, et al. Epigenetic quantification of tumor-infiltrating T-lymphocytes. Epigenetics 2011; 6: 236-46; PMID: 20962591; http://dx. doi. org/10. 4161/epi. 6. 2. 13755.
43. Redjimi N, Raffin C, Raimbaud I, Pignon P, Matsuzaki J, Odunsi K, Valmori D, Ayyoub M. CXCR3C T regulatory cells selectively accumulate in human ovarian carcinomas to limit type I immunity. Cancer Res 2012; 72: 4351-60; PMID: 22798340; http://dx. doi. org/10. 1158/0008-5472. CAN-12-0579.
44. Kryczek I, Liu R, Wang G, Wu K, Shu X, Szeliga W, Vatan L, Finlayson E, Huang E, Simeone D, et al. FOXP3 defines regulatory T cells in human tumor and autoimmune disease. Cancer Res 2009; 69: 3995-4000; PMID: 19383912; http://dx. doi. org/10. 1158/0008-5472. CAN-08-3804.
45. Facciabene A, Peng X, Hagemann IS, Balint K, Barchetti A, Wang LP, Gimotty PA, Gilks CB, Lal P, Zhang L, et al. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature 2011; 475: 226-30; PMID: 21753853; http://dx. doi. org/10. 1038/nature10169.
46. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004; 10: 942-9; PMID: 15322536; http://dx. doi. org/10. 1038/nm1093.
47. Kryczek I, Wei S, Zhu G, Myers L, Mottram P, Cheng P, Chen L, Coukos G, Zou W. Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res 2007; 67: 8900-5; PMID: 17875732; http://dx. doi. org/10. 1158/0008-5472. CAN-07-1866.
48. Giuntoli RL, 2nd, Webb TJ, Zoso A, Rogers O, Diaz-Montes TP, Bristow RE, Oelke M. Ovarian cancerassociated ascites demonstrates altered immune environment: implications for antitumor immunity. Anticancer Res 2009; 29: 2875-84; PMID: 19661290.
49. Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E, Deibl M, Gastl G, Gunsilius E, Marth C. The expression of the regulatory T cellspecific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 2005; 11: 8326-31; PMID: 16322292; http://dx. doi. org/10. 1158/1078-0432. CCR-05-1244.
50. Napoletano C, Bellati F, Landi R, Pauselli S, Marchetti C, Visconti V, Sale P, Liberati M, Rughetti A, Frati L, et al. Ovarian cancer cytoreduction induces changes in T cell population subsets reducing immunosuppression. J Cell Mol Med 2010; 14: 2748-59; PMID: 19780872; http://dx. doi. org/10. 1111/j. 1582-4934. 2009. 00911. x.
51. Fialova A, Partlova S, Sojka L, Hromadkova H, Brtnicky T, Fucikova J, Kocian P, Rob L, Bartunkova J, Spisek R. Dynamics of T-cell infiltration during the course of ovarian cancer: the gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T-cells. Int J Cancer 2013; 132: 1070-9; PMID: 22865582; http://dx. doi. org/10. 1002/ijc. 27759.
52. Polcher M, Braun M, Friedrichs N, Rudlowski C, Bercht E, Fimmers R, Sauerwald A, Keyver-Paik MD, Kubler K, Buttner R, et al. Foxp3(C) cell infiltration and granzyme B(C)/Foxp3(C) cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma. Cancer Immunol Immunother 2010; 59: 909-19; PMID: 20087581; http://dx. doi. org/10. 1007/s00262-010-0817-1.
53. Mhawech-Fauceglia P, Wang D, Ali L, Lele S, Huba MA, Liu S, Odunsi K. Intraepithelial T cells and tumor-associated macrophages in ovarian cancer patients. Cancer Immun 2013; 13: 1; PMID: 23390372.
54. Yigit R, Massuger LF, Figdor CG, Torensma R. Ovarian cancer creates a suppressive microenvironment to escape immune elimination. Gynecol Oncol 2010; 117: 366-72; PMID: 20144842; http://dx. doi. org/10. 1016/j. ygyno. 2010. 01. 019.
55. Yang C, Lee H, Jove V, Deng J, Zhang W, Liu X, Forman S, Dellinger TH, Wakabayashi M, Yu H, et al. Prognostic significance of B-cells and pSTAT3 in patients with ovarian cancer. PloS One 2013; 8: e54029; PMID: 23326565; http://dx. doi. org/10. 1371/journal. pone. 0054029.
56. Nielsen JS, Nelson BH. Tumor-infiltrating B cells and T cells: Working together to promote patient survival. Oncoimmunology 2012; 1: 1623-5; PMID: 23264915; http://dx. doi. org/10. 4161/onci. 21650.
57. Besser MJ, Shapira-Frommer R, Treves AJ, Zippel D, Itzhaki O, Hershkovitz L, Levy D, Kubi A, Hovav E, Chermoshniuk N, et al. Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res 2010; 16: 2646-55; PMID: 20406835; http://dx. doi. org/10. 1158/1078-0432. CCR-10-0041.
58. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002; 298: 850-4; PMID: 12242449; http://dx. doi. org/10. 1126/science. 1076514.
59. Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005; 23: 2346-57; PMID: 15800326; http://dx. doi. org/10. 1200/JCO. 2005. 00. 240.
60. Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol 2008; 26: 5233-9; PMID: 18809613; http://dx. doi. org/10. 1200/JCO. 2008. 16. 5449.
61. Robbins PF, Dudley ME, Wunderlich J, El-Gamil M, Li YF, Zhou J, Huang J, Powell DJ, Jr., Rosenberg SA. Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy. J Immunol 2004; 173: 7125-30; http://dx. doi. org/10. 4049/jimmunol. 173. 12. 7125.
62. Rosenberg SA, Dudley ME. Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr Opin Immunol 2009; 21: 233-40; PMID: 19304471; http://dx. doi. org/10. 1016/j. coi. 2009. 03. 002.
63. Freedman RS, Tomasovic B, Templin S, Atkinson EN, Kudelka A, Edwards CL, Platsoucas CD. Largescale expansion in interleukin-2 of tumor-infiltrating lymphocytes from patients with ovarian carcinoma for adoptive immunotherapy. J Immunol Methods 1994; 167: 145-60; PMID: 8308273; http://dx. doi. org/10. 1016/0022-1759(94)90084-1.
64. Dudley ME, Wunderlich JR, Shelton TE, Even J, Rosenberg SA. Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother 2003; 26: 332-42; PMID: 12843795; http://dx. doi. org/10. 1097/00002371-200307000-00005.
65. Aoki Y, Takakuwa K, Kodama S, Tanaka K, Takahashi M, Tokunaga A, Takahashi T. 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: 1934-9; PMID: 2004379.
66. Freedman RS, Edwards CL, Kavanagh JJ, Kudelka AP, Katz RL, Carrasco CH, Atkinson EN, Scott W, Tomasovic B, Templin S, 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; PMID: 7834119; http://dx. doi. org/10. 1097/00002371-199410000-00004.
67. Ikarashi H, Fujita K, Takakuwa K, Kodama S, Tokunaga A, Takahashi T, Tanaka K. Immunomodulation in patients with epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Cancer Res 1994; 54: 190-6; PMID: 8261438.
68. Fujita K, Ikarashi H, Takakuwa K, Kodama S, Tokunaga A, Takahashi T, Tanaka K. Prolonged diseasefree period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Clin Cancer Res 1995; 1: 501-7; PMID: 9816009.
69. Freedman RS, Kudelka AP, Kavanagh JJ, Verschraegen C, Edwards CL, Nash M, Levy L, Atkinson EN, Zhang HZ, Melichar B, et al. 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: 2268-78; PMID: 10873077.
70. Wright SE, Rewers-Felkins KA, Quinlin IS, Phillips CA, Townsend M, Philip R, Dobrzanski MJ, Lockwood-Cooke PR, Robinson W. Cytotoxic T-lymphocyte immunotherapy for ovarian cancer: a pilot study. J Immunother 2012; 35: 196-204; PMID: 22306908; http://dx. doi. org/10. 1097/CJI. 0b013e318243f213.
71. Ye Q, Song D, Poussin M, Yamamoto T, Best A, Li C, Coukos G, Powell DJ, Jr. CD137 accurately identifies and enriches for naturally-occurring tumor-reactive T cells in tumor. Clin Cancer Res 2013: 44-55.
72. Gattinoni L, Finkelstein SE, Klebanoff CA, Antony PA, Palmer DC, Spiess PJ, Hwang LN, Yu Z, Wrzesinski C, Heimann DM, et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8C T cells. J Exp Med 2005; 202: 907-12; PMID: 16203864; http://dx. doi. org/10. 1084/jem. 20050732.
73. Ye Q, Loisiou M, Levine BL, Suhoski MM, Riley JL, June CH, Coukos G, Powell DJ, Jr. Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes. J Translat Med 2011; 9: 131; PMID: 21827675; http://dx. doi. org/10. 1186/1479-5876-9-131.
74. 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: 116-28; PMID: 8954611; http://dx. doi. org/10. 1006/cimm. 1996. 0301.
75. Ino K. Indoleamine 2, 3-dioxygenase and immune tolerance in ovarian cancer. Curr Opin Obstet Gynecol 2011; 23: 13-8; PMID: 20930628; http://dx. doi. org/10. 1097/GCO. 0b013e3283409c79.
76. Wang D, Saga Y, Mizukami H, Sato N, Nonaka H, Fujiwara H, Takei Y, Machida S, Takikawa O, Ozawa K, et al. Indoleamine-2, 3-dioxygenase, an immunosuppressive enzyme that inhibits natural killer cell function, as a useful target for ovarian cancer therapy. Int J Oncol 2012; 40: 929-34; PMID: 22179492.
77. Qian F, Villella J, Wallace PK, Mhawech-Fauceglia P, Tario JD, Jr., Andrews C, Matsuzaki J, Valmori D, Ayyoub M, Frederick PJ, et al. Efficacy of levo-1-methyl tryptophan and dextro-1-methyl tryptophan in reversing indoleamine-2, 3-dioxygenase-mediated arrest of T-cell proliferation in human epithelial ovarian cancer. Cancer Res 2009; 69: 5498-504; PMID: 19491279; http://dx. doi. org/10. 1158/0008-5472. CAN-08-2106.
78. Conejo-Garcia JR, Benencia F, Courreges MC, Gimotty PA, Khang E, Buckanovich RJ, Frauwirth KA, Zhang L, Katsaros D, Thompson CB, et al. Ovarian carcinoma expresses the NKG2D ligand Letal and promotes the survival and expansion of CD28-antitumor T cells. Cancer Res 2004; 64: 2175-82; PMID: 15026360; http://dx. doi. org/10. 1158/0008-5472. CAN-03-2194.
79. Buckanovich RJ, Facciabene A, Kim S, Benencia F, Sasaroli D, Balint K, Katsaros D, O'Brien-Jenkins A, Gimotty PA, Coukos G. Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy. Nat Med 2008; 14: 28-36; PMID: 18157142; http://dx. doi. org/10. 1038/nm1699.
80. Kandalaft LE, Facciabene A, Buckanovich RJ, Coukos G. Endothelin B receptor, a new target in cancer immune therapy. Clin Cancer Res 2009; 15: 4521-8; PMID: 19567593; http://dx. doi. org/10. 1158/1078-0432. CCR-08-0543.
81. Milne K, Barnes RO, Girardin A, Mawer MA, Nesslinger NJ, Ng A, Nielsen JS, Sahota R, Tran E, Webb JR, et al. Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer. PloS One 2008; 3: e3409; PMID: 18923710; http://dx. doi. org/10. 1371/journal. pone. 0003409.
82. Marth C, Fiegl H, Zeimet AG, Muller-Holzner E, Deibl M, Doppler W, Daxenbichler G. Interferongamma expression is an independent prognostic factor in ovarian cancer. Am J Obstet Gynecol 2004; 191: 1598-605; PMID: 15547530; http://dx. doi. org/10. 1016/j. ajog. 2004. 05. 007.
83. 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. Human Pathol 1997; 28: 321-31; PMID: 9042797; http://dx. doi. org/10. 1016/S0046-8177(97)90131-3.
84. Rodriguez GC, Haisley C, Hurteau J, Moser TL, Whitaker R, Bast RC, Jr., Stack MS. Regulation of invasion of epithelial ovarian cancer by transforming growth factor-b. Gynecol Oncol 2001; 80: 245-53; PMID: 11161867; http://dx. doi. org/10. 1006/gyno. 2000. 6042.
85. Nash MA, Lenzi R, Edwards CL, Kavanagh JJ, Kudelka AP, Verschraegen CF, Platsoucas CD, Freedman RS. 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: 172-80; PMID: 9649178; http://dx. doi. org/10. 1046/j. 1365-2249. 1998. 00576. x.
86. Santin AD, Hermonat PL, Ravaggi A, Bellone S, Roman JJ, Smith CV, Pecorelli S, Radominska-Pandya A, Cannon MJ, Parham GP. 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: 254-61; PMID: 11408737; http://dx. doi. org/10. 1159/000058060.
87. Ye Q, Loisiou M, Levine BL, Suhoski MM, Riley JL, June CH, Coukos G, Powell DJ, Jr. Engineered Artificial Antigen Presenting Cells Facilitate Direct and Efficient Expansion of Tumor Infiltrating Lymphocytes. J Transl Med 2011; 9: 131; PMID: 21827675; http://dx. doi. org/10. 1186/1479-5876-9-131.
88. Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P, Brumlik M, Cheng P, Curiel T, Myers L, et al. B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 2006; 203: 871-81; PMID: 16606666; http://dx. doi. org/10. 1084/jem. 20050930.
89. Dangaj D, Lanitis E, Zhao A, Joshi S, Cheng Y, Sandaltzopoulos R, Ra HJ, Danet-Desnoyers G, Powell DJ, Jr., Scholler N. Novel recombinant human b7-h4 antibodies overcome tumoral immune escape to potentiate T-cell antitumor responses. Cancer Res 2013; 73: 4820-9; PMID: 23722540; http://dx. doi. org/10. 1158/0008-5472. CAN-12-3457.
90. Cheng L, Jiang J, Gao R, Wei S, Nan F, Li S, Kong B. B7-H4 expression promotes tumorigenesis in ovarian cancer. Int J Gynecol Cancer 2009; 19: 1481-6; PMID: 19955922; http://dx. doi. org/10. 1111/IGC. 0b013e3181ad0fa2.
91. Simon I, Katsaros D, Rigault de la Longrais I, Massobrio M, Scorilas A, Kim NW, Sarno MJ, Wolfert RL, Diamandis EP. B7-H4 is overexpressed in early-stage ovarian cancer and is independent of CA125 expression. Gynecol Oncol 2007; 106: 334-41; PMID: 17498784; http://dx. doi. org/10. 1016/j. ygyno. 2007. 03. 035.
92. Cubillos-Ruiz JR, Martinez D, Scarlett UK, Rutkowski MR, Nesbeth YC, Camposeco-Jacobs AL, Conejo-Garcia JR. CD277 is a negative co-stimulatory molecule universally expressed by ovarian cancer microenvironmental cells. Oncotarget 2010; 1: 329-38; PMID: 21113407.
93. Riley JL, June CH. The road to recovery: translating PD-1 biology into clinical benefit. Trends Immunol 2007; 28: 48-50; PMID: 17188572; http://dx. doi. org/10. 1016/j. it. 2006. 12. 001.
94. Bennett F, Luxenberg D, Ling V, Wang IM, Marquette K, Lowe D, Khan N, Veldman G, Jacobs KA, Valge-Archer VE, et al. Program death-1 engagement upon TCR activation has distinct effects on costimulation and cytokine-driven proliferation: attenuation of ICOS, IL-4, and IL-21, but not CD28, IL-7, and IL-15 responses. J Immunol 2003; 170: 711-8; http://dx. doi. org/10. 4049/jimmunol. 170. 2. 711.
95. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002; 8: 793-800; PMID: 12091876; http://dx. doi. org/10. 1038/nm0902-1039c.
96. Zhang L, Gajewski TF, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood 2009; 114: 1545-52; PMID: 19417208; http://dx. doi. org/10. 1182/blood-2009-03-206672.
97. Matsuzaki J, Gnjatic S, Mhawech-Fauceglia P, Beck A, Miller A, Tsuji T, Eppolito C, Qian F, Lele S, Shrikant P, et al. Tumor-infiltrating NY-ESO-1-specific CD8C T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proc Natl Acad Sci U S A 2010; 107: 7875-80; PMID: 20385810; http://dx. doi. org/10. 1073/pnas. 1003345107.
98. Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M, Rietz C, Flies DB, Lau JS, Zhu G, et al. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 2005; 65: 1089-96; PMID: 15705911.
99. Krempski J, Karyampudi L, Behrens MD, Erskine CL, Hartmann L, Dong H, Goode EL, Kalli KR, Knutson KL. Tumor-infiltrating programmed death receptor-1C dendritic cells mediate immune suppression in ovarian cancer. J Immunol 2011; 186: 6905-13; http://dx. doi. org/10. 4049/jimmunol. 1100274.
100. Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson KL, Daniel B, Zimmermann MC, et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 2003; 9: 562-7; PMID: 12704383; http://dx. doi. org/10. 1038/nm863.
101. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012; 366: 2455-65; PMID: 22658128; http://dx. doi. org/10. 1056/NEJMoa1200694.
102. Hamanishi J, Mandai M, Ikeda T, Minami M, Kawaguchi A, Noriomi M, Abiko K, Baba T, Yamaguchi K, Ueda A, et al. Efficacy and safety of anti-PD-1 antibody (Nivolumab: BMS-936558, ONO-4538) in patients with platinum-resistant ovarian cancer. J Clin Oncol 2014; 3s; 5s. Supplementary Abstract 5511.
103. Peggs KS, Quezada SA, Korman AJ, Allison JP. Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol 2006; 18: 206-13; PMID: 16464564; http://dx. doi. org/10. 1016/j. coi. 2006. 01. 011.
104. Korman AJ, Peggs KS, Allison JP. Checkpoint blockade in cancer immunotherapy. Adv Immunol 2006; 90: 297-339; PMID: 16730267; http://dx. doi. org/10. 1016/S0065-2776(06)90008-X.
105. Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol 2002; 3: 611-8; PMID: 12087419; http://dx. doi. org/10. 1038/ni0702-611.
106. Hodi FS, Mihm MC, Soiffer RJ, Haluska FG, Butler M, Seiden MV, Davis T, Henry-Spires R, MacRae S, Willman A, 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: 4712-7; PMID: 12682289; http://dx. doi. org/10. 1073/pnas. 0830997100.
107. Grosso JF, Jure-Kunkel MN. CTLA-4 blockade in tumor models: an overview of preclinical and translational research. Cancer Immun 2013; 13: 5; PMID: 23390376.
108. Hodi FS, Butler M, Oble DA, Seiden MV, Haluska FG, Kruse A, Macrae S, Nelson M, Canning C, Lowy I, et al. 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: 3005-10; PMID: 18287062; http://dx. doi. org/10. 1073/pnas. 0712237105.
109. Kandalaft LE, Powell DJ, Jr., Singh N, Coukos G. Immunotherapy for ovarian cancer: what's next? J Clin Oncol 2011; 29: 925-33; PMID: 21079136; http://dx. doi. org/10. 1200/JCO. 2009. 27. 2369.
110. Curran MA, Kim M, Montalvo W, Al-Shamkhani A, Allison JP. Combination CTLA-4 blockade and 4-1BB activation enhances tumor rejection by increasing T-cell infiltration, proliferation, and cytokine production. PloS One 2011; 6: e19499; PMID: 21559358; http://dx. doi. org/10. 1371/journal. pone. 0019499.
111. Duraiswamy J, Kaluza KM, Freeman GJ, Coukos G. Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T-Cell Rejection Function in Tumors. Cancer Res 2013; 73: 3591-603; PMID: 23633484; http://dx. doi. org/10. 1158/0008-5472. CAN-12-4100.
112. Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A 2010; 107: 4275-80; PMID: 20160101; http://dx. doi. org/10. 1073/pnas. 0915174107.
113. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013; 369: 122-33; PMID: 23724867; http://dx. doi. org/10. 1056/NEJMoa1302369.
114. Chiang CL, Kandalaft LE, Tanyi J, Hagemann AR, Motz GT, Svoronos N, Montone K, Mantia-Smaldone GM, Smith L, Nisenbaum HL, et al. A dendritic cell vaccine pulsed with autologous hypochlorous acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside. Clin Cancer Res 2013; 19: 4801-15; PMID: 23838316; http://dx. doi. org/10. 1158/1078-0432. CCR-13-1185.
115. Kandalaft LE, Powell DJ, Jr., Chiang CL, Tanyi J, Kim S, Bosch M, Montone K, Mick R, Levine BL, Torigian DA, et al. Autologous lysate-pulsed dendritic cell vaccination followed by adoptive transfer of vaccine-primed ex vivo co-stimulated T cells in recurrent ovarian cancer. Oncoimmunology 2013; 2: e22664; http://dx. doi. org/10. 4161/onci. 22664.
116. Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol 2010; 37: 508-16; PMID: 21074066; http://dx. doi. org/10. 1053/j. seminoncol. 2010. 09. 008.
117. Guo Z, Cheng D, Xia Z, Luan M, Wu L, Wang G, Zhang S. Combined TIM-3 blockade and CD137 activation affords the long-term protection in a murine model of ovarian cancer. J Translat Med 2013; 11: 215; PMID: 24044888; http://dx. doi. org/10. 1186/1479-5876-11-215.
118. Scarlett UK, Rutkowski MR, Rauwerdink AM, Fields J, Escovar-Fadul X, Baird J, Cubillos-Ruiz JR, Jacobs AC, Gonzalez JL, Weaver J, et al. Ovarian cancer progression is controlled by phenotypic changes in dendritic cells. J Exp Med 2012; 209: 495-506; PMID: 22351930; http://dx. doi. org/10. 1084/jem. 20111413.
119. Lutsiak ME, Semnani RT, De Pascalis R, Kashmiri SV, Schlom J, Sabzevari H. Inhibition of CD4(C) 25C T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 2005; 105: 2862-8; PMID: 15591121; http://dx. doi. org/10. 1182/blood-2004-06-2410.
120. Bracci L, Moschella F, Sestili P, La Sorsa V, Valentini M, Canini I, Baccarini S, Maccari S, Ramoni C, Belardelli F, et al. Cyclophosphamide enhances the antitumor efficacy of adoptively transferred immune cells through the induction of cytokine expression, Bcell and T-cell homeostatic proliferation, and specific tumor infiltration. Clin Cancer Res 2007; 13: 644-53; PMID: 17255288; http://dx. doi. org/10. 1158/1078-0432. CCR-06-1209.
121. Prasad SJ, Farrand KJ, Matthews SA, Chang JH, McHugh RS, Ronchese F. Dendritic cells loaded with stressed tumor cells elicit long-lasting protective tumor immunity in mice depleted of CD4CCD25C regulatory T cells. J Immunol 2005; 174: 90-8; http://dx. doi. org/10. 4049/jimmunol. 174. 1. 90.
122. Rech AJ, Vonderheide RH. Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells. Ann N Y Acad Sci 2009; 1174: 99-106; PMID: 19769742; http://dx. doi. org/10. 1111/j. 1749-6632. 2009. 04939. x.
123. Kreijveld E, Koenen HJ, Klasen IS, Hilbrands LB, Joosten I. Following anti-CD25 treatment, a functional CD4CCD25C regulatory T-cell pool is present in renal transplant recipients. Am J Transplant 2007; 7: 249-55; PMID: 17109733; http://dx. doi. org/10. 1111/j. 1600-6143. 2006. 01604. x.
124. Powell DJ, Jr., Attia P, Ghetie V, Schindler J, Vitetta ES, Rosenberg SA. Partial reduction of human FOXP3C CD4 T cells in vivo after CD25-directed recombinant immunotoxin administration. J Immunother 2008; 31: 189-98; PMID: 18481388; http://dx. doi. org/10. 1097/CJI. 0b013e31815dc0e8.
125. Powell DJ, Jr., Felipe-Silva A, Merino MJ, Ahmadzadeh M, Allen T, Levy C, White DE, Mavroukakis S, Kreitman RJ, Rosenberg SA, et al. Administration of a CD25-directed immunotoxin, LMB-2, to patients with metastatic melanoma induces a selective partial reduction in regulatory T cells in vivo. J Immunol 2007; 179: 4919-28; http://dx. doi. org/10. 4049/jimmunol. 179. 7. 4919.
126. Powell DJ, Jr., Parker LL, Rosenberg SA. Large-scale depletion of CD25C regulatory T cells from patient leukapheresis samples. J Immunother 2005; 28: 403-11; PMID: 16000960; http://dx. doi. org/10. 1097/01. cji. 0000170363. 22585. 5a.
127. Powell DJ, Jr., de Vries CR, Allen T, Ahmadzadeh M, Rosenberg SA. Inability to mediate prolonged reduction of regulatory T Cells after transfer of autologous CD25-depleted PBMC and interleukin-2 after lymphodepleting chemotherapy. J Immunother 2007; 30: 438-47; PMID: 17457218; http://dx. doi. org/10. 1097/CJI. 0b013e3180600ff9.
128. Leveque L, Deknuydt F, Bioley G, Old LJ, Matsuzaki J, Odunsi K, Ayyoub M, Valmori D. Interleukin 2-mediated conversion of ovarian cancer-associated CD4C regulatory T cells into proinflammatory interleukin 17-producing helper T cells. J Immunother 2009; 32: 101-8; PMID: 19238008; http://dx. doi. org/10. 1097/CJI. 0b013e318195b59e.
129. Wallen H, Thompson JA, Reilly JZ, Rodmyre RM, Cao J, Yee C. Fludarabine modulates immune response and extends in vivo survival of adoptively transferred CD8 T cells in patients with metastatic melanoma. PloS One 2009; 4: e4749; PMID: 19270751; http://dx. doi. org/10. 1371/journal. pone. 0004749.
130. Muranski P, Boni A, Wrzesinski C, Citrin DE, Rosenberg SA, Childs R, Restifo NP. Increased intensity lymphodepletion and adoptive immunotherapy-how far can we go? Nat Clin Pract Oncol 2006; 3: 668-81; PMID: 17139318; http://dx. doi. org/10. 1038/ncponc0666.
131. Liao JB, Disis ML. Therapeutic vaccines for ovarian cancer. Gynecol Oncol 2013; 130 (3): 667-73.
132. Canevari S, Stoter G, Arienti F, Bolis G, Colnaghi MI, Di Re EM, Eggermont AM, Goey SH, Gratama JW, Lamers CH, et al. Regression of advanced ovarian carcinoma by intraperitoneal treatment with autologous T lymphocytes retargeted by a bispecific monoclonal antibody. J Natl Cancer Institute 1995; 87: 1463-9; PMID: 7674333; http://dx. doi. org/10. 1093/jnci/87. 19. 1463.
133. Cannon MJ, O'Brien TJ. Cellular immunotherapy for ovarian cancer. Expert Opin Biol Ther 2009; 9: 677-88; PMID: 19456205; http://dx. doi. org/10. 1517/14712590902932897.
134. Beller U, Chachoua A, Speyer JL, Sorich J, Dugan M, Liebes L, Hayes R, Beckman EM. Phase IB study of low-dose intraperitoneal recombinant interleukin-2 in patients with refractory advanced ovarian cancer: rationale and preliminary report. Gynecol Oncol 1989; 34: 407-12; PMID: 2788602; http://dx. doi. org/10. 1016/0090-8258(89)90182-0.
135. Bertoglio S, Melioli G, Baldini E, Catturich A, Sertoli MR, Civalleri D, Percivale P, Meier W, Galazka A, Badellino F. Intraperitoneal infusion of recombinant interleukin-2 in malignant ascites in patients with gastrointestinal and ovarian cancer. Acta Med Austriaca 1989; 16: 81-3; PMID: 2609918.
136. Chapman PB, Kolitz JE, Hakes TB, Gabrilove JL, Welte K, Merluzzi VJ, Engert A, Bradley EC, Konrad M, Mertelsmann R. A phase I trial of intraperitoneal recombinant interleukin 2 in patients with ovarian carcinoma. Invest New Drugs 1988; 6: 179-88; PMID: 3263958; http://dx. doi. org/10. 1007/BF00175395.
137. Lotze MT, Custer MC, Rosenberg SA. Intraperitoneal administration of interleukin-2 in patients with cancer. Arch Surg 1986; 121: 1373-9; PMID: 3491595; http://dx. doi. org/10. 1001/archsurg. 1986. 01400120019002.
138. Vlad AM, Budiu RA, Lenzner DE, Wang Y, Thaller JA, Colonello K, Crowley-Nowick PA, Kelley JL, Price FV, Edwards RP. A phase II trial of intraperitoneal interleukin-2 in patients with platinum-resistant or platinum-refractory ovarian cancer. Cancer Immunol Immunother 2010; 59: 293-301; PMID: 19690855; http://dx. doi. org/10. 1007/s00262-009-0750-3.
139. Lanitis E, Smith JB, Dangaj D, Flingai S, Poussin M, Xu S, Czerniecki BJ, Li YF, Robbins PF, Powell DJ, Jr. A human ErbB2-specific T-cell receptor confers potent antitumor effector functions in genetically engineered primary cytotoxic lymphocytes. Hum Gene Ther 2014; 25: 730-9; PMID: 25003657; http://dx. doi. org/10. 1089/hum. 2014. 006.
140. Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 2011; 29: 917-24; PMID: 21282551; http://dx. doi. org/10. 1200/JCO. 2010. 32. 2537.
141. Parker LL, Do MT, Westwood JA, Wunderlich JR, Dudley ME, Rosenberg SA, Hwu P. Expansion and characterization of T cells transduced with a chimeric receptor against ovarian cancer. Hum Gene Ther 2000; 11: 2377-87; PMID: 11096442; http://dx. doi. org/10. 1089/104303400750038480.
142. Kershaw MH, Westwood JA, Parker LL, Wang G, Eshhar Z, Mavroukakis SA, White DE, Wunderlich JR, Canevari S, Rogers-Freezer L, et al. A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res 2006; 12: 6106-15; PMID: 17062687; http://dx. doi. org/10. 1158/1078-0432. CCR-06-1183.
143. Song DG, Ye Q, Carpenito C, Poussin M, Wang LP, Ji C, Figini M, June CH, Coukos G, Powell DJ, Jr. In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4-1BB). Cancer Res 2011; 71: 4617-27; PMID: 21546571; http://dx. doi. org/10. 1158/0008-5472. CAN-11-0422.
144. Kandalaft LE, Powell DJ, Jr., Coukos G. A phase I clinical trial of adoptive transfer of folate receptor-a redirected autologous T cells for recurrent ovarian cancer. J Translat Med 2012; 10: 157; PMID: 22863016; http://dx. doi. org/10. 1186/1479-5876-10-157.
145. Carpenito C, Milone MC, Hassan R, Simonet JC, Lakhal M, Suhoski MM, Varela-Rohena A, Haines KM, Heitjan DF, Albelda SM, et al. Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc Natl Acad Sci U S A 2009; 106: 3360-5; PMID: 19211796; http://dx. doi. org/10. 1073/pnas. 0813101106.
146. Song DG, Ye Q, Poussin M, Harms GM, Figini M, Powell DJ, Jr. CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo. Blood 2012; 119: 696-706; PMID: 22117050; http://dx. doi. org/10. 1182/blood-2011-03-344275.
147. Chekmasova AA, Brentjens RJ. Adoptive T cell immunotherapy strategies for the treatment of patients with ovarian cancer. Discov Med 2010; 9: 62-70; PMID: 20102688.
148. Lanitis E, Dangaj D, Hagemann IS, Song DG, Best A, Sandaltzopoulos R, Coukos G, Powell DJ, Jr. Primary human ovarian epithelial cancer cells broadly express HER2 at immunologically-detectable levels. PloS One 2012; 7: e49829; PMID: 23189165; http://dx. doi. org/10. 1371/journal. pone. 0049829.
149. Spear P, Barber A, Sentman CL. Collaboration of chimeric antigen receptor (CAR)-expressing T cells and host T cells for optimal elimination of established ovarian tumors. Oncoimmunology 2013; 2: e23564; PMID: 23734311; http://dx. doi. org/10. 4161/onci. 23564.