Monitoring regulatory immune responses in tumor immunotherapy clinical trials

Frontiers in Oncology

Volumn 3 MAY, Issue , 2013, Pages

  Olson, Brian M ^a   McNeel, Douglas G ^a  

^a UNIVERSITY OF WISCONSIN   (United States)

Author keywords

Immune monitoring; Myeloid derived suppressor cells; Predictors of response; Regulatory T cells; Suppression; Tolerance

Indexed keywords

ANTIGEN PRESENTING CELL VACCINE; CD11B ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DENDRITIC CELL VACCINE; INDOLEAMINE 2, 3 DIOXYGENASE; INTERLEUKIN 10; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 35; IPILIMUMAB; PEPTIDE VACCINE; SIPULEUCEL T; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; TUMOR CELL VACCINE; UNCLASSIFIED DRUG; VACCINE; VIRUS VACCINE;

ADJUVANT THERAPY; BONE MARROW CELL; BREAST CANCER; CANCER IMMUNOTHERAPY; CELL COUNT; CHRONIC LYMPHATIC LEUKEMIA; COLORECTAL CANCER; GLIOBLASTOMA; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL MONITORING; IMMUNOREGULATION; KIDNEY CANCER; LOW DRUG DOSE; LUNG CANCER; MELANOMA; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROSTATE CANCER; REGULATORY T LYMPHOCYTE; REVIEW; SARCOMA; STOMACH CANCER; SUPPRESSOR CELL; TREATMENT RESPONSE; TUMOR ASSOCIATED LEUKOCYTE;

EID: 84886486434     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2013.00109     Document Type: Review

References (101)

1. Addey, C., White, M., Dou, L., Coe, D., Dyson, J., and Chai, J. G. (2011). Functional plasticity of antigen-specific regulatory T cells in context of tumor. J. Immunol. 186, 4557-4564.
2. Akin, Y., Koksoy, S., Yucel, S., Erdogru, T., and Baykara, M. (2011). Increased peripheral CD4+CD25high Treg in prostate cancer patients is correlated with PSA. Saudi Med. J. 32, 1003-1008.
3. Andersen, M. H., Sorensen, R. B., Brimnes, M. K., Svane, I. M., Becker, J. C., and Thor Straten, P. (2009). Identification of heme oxygenase-1-specific regulatory CD8+ T cells in cancer patients. J. Clin. Invest. 119, 2245-2256.
4. Berntsen, A., Brimnes, M. K., Thor Straten, P., and Svane, I. M. (2010). Increase of circulating CD4+CD25highFoxp3+ regulatory T cells in patients with metastatic renal cell carcinoma during treatment with dendritic cell vaccination and low-dose interleukin-2. J. Immunother. 33, 425-434.
5. Betts, G. J., Clarke, S. L., Richards, H. E., Godkin, A. J., and Gallimore, A. M. (2006). Regulating the immune response to tumours. Adv. Drug Deliv. Rev. 58, 948-961.
6. Beyer, M., Kochanek, M., Darabi, K., Popov, A., Jensen, M., Endl, E., et al. (2005). Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood 106, 2018-2025.
7. Biswas, S. K., and Mantovani, A. (2010). Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat. Immunol. 11, 889-896.
8. Bjoern, J., Brimnes, M. K., Andersen, M. H., Thor Straten, P., and Svane, I. M. (2011). Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2. Scand. J. Immunol. 73, 222-233.
9. Bluestone, J. A., Mackay, C. R., O'Shea, J. J., and Stockinger, B. (2009). The functional plasticity of T cell subsets. Nat. Rev. Immunol. 9, 811-816.
10. Bonertz, A., Weitz, J., Pietsch, D. H., Rahbari, N. N., Schlude, C., Ge, Y., et al. (2009). Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma. J. Clin. Invest. 119, 3311-3321.
11. Bottazzi, B., Polentarutti, N., Acero, R., Balsari, A., Boraschi, D., Ghezzi, P., et al. (1983). Regulation of the macrophage content of neoplasms by chemoattractants. Science 220, 210-212.
12. Bronte, V., and Zanovello, P. (2005). Regulation of immune responses by L-arginine metabolism. Nat. Rev. Immunol. 5, 641-654.
13. Cai, J., Lee, J., Jankowska-Gan, E., Derks, R., Pool, J., Mutis, T., et al. (2004). Minor H antigen HA-1-specific regulator and effector CD8+ T cells, and HA-1 microchimerism, in allograft tolerance. J. Exp. Med. 199, 1017-1023.
14. Carrodeguas, L., Orosz, C. G., Waldman, W. J., Sedmak, D. D., Adams, P. W., and Vanbuskirk, A. M. (1999). Trans vivo analysis of human delayed-type hypersensitivity reactivity. Hum. Immunol. 60, 640-651.
15. Chakraborty, N. G., Chattopadhyay, S., Mehrotra, S., Chhabra, A., and Mukherji, B. (2004). Regulatory T-cell response and tumor vaccine-induced cytotoxic T lymphocytes in human melanoma. Hum. Immunol. 65, 794-802.
16. Chaput, N., Louafi, S., Bardier, A., Charlotte, F., Vaillant, J. C., Menegaux, F., et al. (2009). Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue. Gut 58, 520-529.
17. Chen, Y., Kuchroo, V. K., Inobe, J., Hafler, D. A., and Weiner, H. L. (1994). Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 265, 1237-1240.
18. Coffelt, S. B., Hughes, R., and Lewis, C. E. (2009). Tumor-associated macrophages: effectors of angiogenesis and tumor progression. Biochim. Biophys. Acta 1796, 11-18.
19. Collison, L. W., Chaturvedi, V., Henderson, A. L., Giacomin, P. R., Guy, C., Bankoti, J., et al. (2010). IL-35-mediated induction of a potent regulatory T cell population. Nat. Immunol. 11, 1093-1101.
20. Collison, L. W., Workman, C. J., Kuo, T. T., Boyd, K., Wang, Y., Vignali, K. M., et al. (2007). The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450, 566-569.
21. Correale, P., Rotundo, M. S., Del Vecchio, M. T., Remondo, C., Migali, C., Ginanneschi, C., et al. (2010). Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy. J. Immunother. 33, 435-441.
22. Cortesini, R., Lemaoult, J., Ciubotariu, R., and Cortesini, N. S. (2001). CD8+CD28-T suppressor cells and the induction of antigen-specific, antigen-presenting cell-mediated suppression of Th reactivity. Immunol. Rev. 182, 201-206.
23. Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., et al. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 10, 942-949.
24. Di Nicola, M., Zappasodi, R., Carlo-Stella, C., Mortarini, R., Pupa, S. M., Magni, M., et al. (2009). Vaccination with autologous tumor-loaded dendritic cells induces clinical and immunologic responses in indolent B-cell lymphoma patients with relapsed and measurable disease: a pilot study. Blood 113, 18-27.
25. Finkelstein, S. E., Iclozan, C., Bui, M. M., Cotter, M. J., Ramakrishnan, R., Ahmed, J., et al. (2012). Combination of external beam radiotherapy (EBRT) with intratumoral injection of dendritic cells as neo-adjuvant treatment of high-risk soft tissue sarcoma patients. Int. J. Radiat. Oncol. Biol. Phys. 82, 924-932.
26. Fong, B., Jin, R., Wang, X., Safaee, M., Lisiero, D. N., Yang, I., et al. (2012). Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients. PLoS ONE 7:e32614. doi:10.1371/journal.pone.0032614
27. Francois, V., Ottaviani, S., Renkvist, N., Stockis, J., Schuler, G., Thielemans, K., et al. (2009). The CD4(+) T-cell response of melanoma patients to a MAGE-A3 peptide vaccine involves potential regulatory T cells. Cancer Res. 69, 4335-4345.
28. Gabrilovich, D. I., and Nagaraj, S. (2009). Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 9, 162-174.
29. Gates, J. D., Clifton, G. T., Benavides, L. C., Sears, A. K., Carmichael, M. G., Hueman, M. T., et al. (2010). Circulating regulatory T cells (CD4+CD25+FOXP3+) decrease in breast cancer patients after vaccination with a modified MHC class II HER2/neu (AE37) peptide. Vaccine 28, 7476-7482.
30. Gershon, R. K., and Kondo, K. (1970). Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology 18, 723-737.
31. Gershon, R. K., and Kondo, K. (1971). Infectious immunological tolerance. Immunology 21, 903-914.
32. Gnjatic, S., Altorki, N. K., Tang, D. N., Tu, S. M., Kundra, V., Ritter, G., et al. (2009). NY-ESO-1 DNA vaccine induces T-cell responses that are suppressed by regulatory T cells. Clin. Cancer Res. 15, 2130-2139.
33. Groux, H., O'Garra, A., Bigler, M., Rouleau, M., Antonenko, S., De Vries, J. E., et al. (1997). A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389, 737-742.
34. Gulley, J. L., Arlen, P. M., Madan, R. A., Tsang, K. Y., Pazdur, M. P., Skarupa, L., et al. (2010). Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol. Immunother. 59, 663-674.
35. Hadaschik, B., Su, Y., Huter, E., Ge, Y., Hohenfellner, M., and Beckhove, P. (2012). Antigen specific T-Cell responses against tumor antigens are controlled by regulatory T cells in patients with prostate cancer. J. Urol. 187, 1458-1465.
36. Hamid, O., Schmidt, H., Nissan, A., Ridolfi, L., Aamdal, S., Hansson, J., et al. (2011). A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. J. Transl. Med. 9, 204.
37. Heckel, M. C., Wolfson, A., Slachta, C. A., Schwarting, R., Salgame, P., Katsetos, C. D., et al. (2011). Human breast tumor cells express IL-10 and IL-12p40 transcripts and proteins, but do not produce IL-12p70. Cell. Immunol. 266, 143-153.
38. Heusinkveld, M., and van der Burg, S. H. (2011). Identification and manipulation of tumor associated macrophages in human cancers. J. Transl. Med. 9, 216.
39. Hiraoka, N., Onozato, K., Kosuge, T., and Hirohashi, S. (2006). Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin. Cancer Res. 12, 5423-5434.
40. Hodi, F. S., O'Day, S. J., Mcdermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., et al. (2010). Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711-723.
41. Huang, B., Pan, P. Y., Li, Q., Sato, A. I., Levy, D. E., Bromberg, J., et al. (2006). Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res. 66, 1123-1131.
42. Hus, I., Schmitt, M., Tabarkiewicz, J., Radej, S., Wojas, K., Bojarska-Junak, A., et al. (2008). Vaccination of B-CLL patients with autologous dendritic cells can change the frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+ regulatory T cells toward an antileukemia response. Leukemia 22, 1007-1017.
43. Jordan, M. S., Boesteanu, A., Reed, A. J., Petrone, A. L., Holenbeck, A. E., Lerman, M. A., et al. (2001). Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2, 301-306.
44. Kantoff, P. W., Higano, C. S., Shore, N. D., Berger, E. R., Small, E. J., Penson, D. F., et al. (2010). Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363, 411-422.
45. Katz, S. C., Bamboat, Z. M., Maker, A. V., Shia, J., Pillarisetty, V. G., Yopp, A. C., et al. (2013). Regulatory T cell infiltration predicts outcome following resection of colorectal cancer liver metastases. Ann. Surg. Oncol. 20, 946-955.
46. Kavanagh, B., O'Brien, S., Lee, D., Hou, Y., Weinberg, V., Rini, B., et al. (2008). CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion. Blood 112, 1175-1183.
47. Kiniwa, Y., Miyahara, Y., Wang, H. Y., Peng, W., Peng, G., Wheeler, T. M., et al. (2007). CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer. Clin. Cancer Res. 13, 6947-6958.
48. Kobayashi, N., Hiraoka, N., Yamagami, W., Ojima, H., Kanai, Y., Kosuge, T., et al. (2007). FOXP3+ regulatory T cells affect the development and progression of hepatocarcinogenesis. Clin. Cancer Res. 13, 902-911.
49. Kono, K., Kawaida, H., Takahashi, A., Sugai, H., Mimura, K., Miyagawa, N., et al. (2006). CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol. Immunother. 55, 1064-1071.
50. Kusmartsev, S., Nefedova, Y., Yoder, D., and Gabrilovich, D. I. (2004). Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J. Immunol. 172, 989-999.
51. Lehe, C., Ghebeh, H., Al-Sulaiman, A., Al Qudaihi, G., Al-Hussein, K., Almohareb, F., et al. (2008). The Wilms' tumor antigen is a novel target for human CD4+ regulatory T cells: implications for immunotherapy. Cancer Res. 68, 6350-6359.
52. Levings, M. K., Gregori, S., Tresoldi, E., Cazzaniga, S., Bonini, C., and Roncarolo, M. G. (2005). Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood 105, 1162-1169.
53. Liakou, C. I., Kamat, A., Tang, D. N., Chen, H., Sun, J., Troncoso, P., et al. (2008). CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc. Natl. Acad. Sci. U.S.A. 105, 14987-14992.
54. Lissoni, P., Brivio, F., Fumagalli, L., Messina, G., Meregalli, S., Porro, G., et al. (2009). Effects of the conventional antitumor therapies surgery, chemotherapy, radiotherapy and immunotherapy on regulatory T lymphocytes in cancer patients. Anticancer Res. 29, 1847-1852.
55. Liu, V. C., Wong, L. Y., Jang, T., Shah, A. H., Park, I., Yang, X., et al. (2007). Tumor evasion of the immune system by converting CD4+CD25-T cells into CD4+CD25+ T regulatory cells: role of tumor-derived TGF-beta. J. Immunol. 178, 2883-2892.
56. Liyanage, U. K., Moore, T. T., Joo, H. G., Tanaka, Y., Herrmann, V., Doherty, G., et al. (2002). Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J. Immunol. 169, 2756-2761.
57. Lohr, J., Knoechel, B., and Abbas, A. K. (2006). Regulatory T cells in the periphery. Immunol. Rev. 212, 149-162.
58. Mantovani, A., Sozzani, S., Locati, M., Allavena, P., and Sica, A. (2002). Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 23, 549-555.
59. Mazzoni, A., Bronte, V., Visintin, A., Spitzer, J. H., Apolloni, E., Serafini, P., et al. (2002). Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. J. Immunol. 168, 689-695.
60. Mellor, A. L., and Munn, D. H. (2004). IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol. 4, 762-774.
61. Miller, A. M., Lundberg, K., Ozenci, V., Banham, A. H., Hellstrom, M., Egevad, L., et al. (2006). CD4+CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J. Immunol. 177, 7398-7405.
62. Montero, A. J., Diaz-Montero, C. M., Kyriakopoulos, C. E., Bronte, V., and Mandruzzato, S. (2012). Myeloid-derived suppressor cells in cancer patients: a clinical perspective. J. Immunother. 35, 107-115.
63. Mougiakakos, D., Choudhury, A., Lladser, A., Kiessling, R., and Johansson, C. C. (2010). Regulatory T cells in cancer. Adv. Cancer Res. 107, 57-117.
64. Movahedi, K., Guilliams, M., Van Den Bossche, J., Van Den Bergh, R., Gysemans, C., Beschin, A., et al. (2008). Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 111, 4233-4244.
65. Nagaraj, S., Gupta, K., Pisarev, V., Kinarsky, L., Sherman, S., Kang, L., et al. (2007). Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat. Med. 13, 828-835.
66. Olson, B. M., Jankowska-Gan, E., Becker, J. T., Vignali, D. A., Burlingham, W. J., and Mcneel, D. G. (2012). Human prostate tumor antigen-specific CD8+ regulatory T cells are inhibited by CTLA-4 or IL-35 blockade. J. Immunol. 189, 5590-5601.
67. O'Mahony, D., Morris, J. C., Quinn, C., Gao, W., Wilson, W. H., Gause, B., et al. (2007). A pilot study of CTLA-4 blockade after cancer vaccine failure in patients with advanced malignancy. Clin. Cancer Res. 13, 958-964.
68. Pages, F., Galon, J., Dieu-Nosjean, M. C., Tartour, E., Sautes-Fridman, C., and Fridman, W. H. (2010). Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 29, 1093-1102.
69. Peranzoni, E., Zilio, S., Marigo, I., Dolcetti, L., Zanovello, P., Mandruzzato, S., et al. (2010). Myeloid-derived suppressor cell heterogeneity and subset definition. Curr. Opin. Immunol. 22, 238-244.
70. Pohla, H., Buchner, A., Stadlbauer, B., Frankenberger, B., Stevanovic, S., Walter, S., et al. (2013). High immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination. Mol. Med. 18, 1499-1508.
71. Polansky, J. K., Kretschmer, K., Freyer, J., Floess, S., Garbe, A., Baron, U., et al. (2008). DNA methylation controls Foxp3 gene expression. Eur. J. Immunol. 38, 1654-1663.
72. Prins, R. M., Wang, X., Soto, H., Young, E., Lisiero, D. N., Fong, B., et al. (2013). Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients. J. Immunother. 36, 152-157.
73. Qin, S., Cobbold, S. P., Pope, H., Elliott, J., Kioussis, D., Davies, J., et al. (1993). "Infectious" transplantation tolerance. Science 259, 974-977.
74. Read, S., Malmstrom, V., and Powrie, F. (2000). Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J. Exp. Med. 192, 295-302.
75. Roncarolo, M. G., Bacchetta, R., Bordignon, C., Narula, S., and Levings, M. K. (2001). Type 1 T regulatory cells. Immunol. Rev. 182, 68-79.
76. Santegoets, S. J., Stam, A. G., Lougheed, S. M., Gall, H., Scholten, P. E., Reijm, M., et al. (2013). T cell profiling reveals high CD4(+)CTLA-4 (+) T cell frequency as dominant predictor for survival after Prostate GVAX/ipilimumab treatment. Cancer Immunol. Immunother. 62, 245-256.
77. Sarantopoulos, S., Lu, L., and Cantor, H. (2004). Qa-1 restriction of CD8+ suppressor T cells. J. Clin. Invest. 114, 1218-1221.
78. Schwarzer, A., Wolf, B., Fisher, J. L., Schwaab, T., Olek, S., Baron, U., et al. (2012). Regulatory T-cells and associated pathways in metastatic renal cell carcinoma (mRCC) patients undergoing DC-vaccination and cytokine-therapy. PLoS ONE 7:e46600. doi:10.1371/journal.pone.0046600
79. Serafini, P., Mgebroff, S., Noonan, K., and Borrello, I. (2008). Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res. 68, 5439-5449.
80. Shafer-Weaver, K. A., Anderson, M. J., Stagliano, K., Malyguine, A., Greenberg, N. M., and Hurwitz, A. A. (2009). Cutting edge: tumor-specific CD8+ T cells infiltrating prostatic tumors are induced to become suppressor cells. J. Immunol. 183, 4848-4852.
81. Takahashi, T., Tagami, T., Yamazaki, S., Uede, T., Shimizu, J., Sakaguchi, N., et al. (2000). Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med. 192, 303-310.
82. Tarhini, A., Edington, H., Butterfield, L., Tawbi, H., Moschos, S., Shuai, Y., et al. (2012). "Neoadjuvant ipilimumab in locally/regionally advanced melanoma: clinical outcome and immune monitoring," in 2012 ASCO Annual Meeting, Chicago, Abstract 8533.
83. Valzasina, B., Piconese, S., Guiducci, C., and Colombo, M. P. (2006). Tumor-induced expansion of regulatory T cells by conversion of CD4+CD25-lymphocytes is thymus and proliferation independent. Cancer Res. 66, 4488-4495.
84. van der Burg, S. H., Piersma, S. J., De Jong, A., Van Der Hulst, J. M., Kwappenberg, K. M., Van Den Hende, M., et al. (2007). Association of cervical cancer with the presence of CD4+ regulatory T cells specific for human papillomavirus antigens. Proc. Natl. Acad. Sci. U.S.A. 104, 12087-12092.
85. VanBuskirk, A. M., Burlingham, W. J., Jankowska-Gan, E., Chin, T., Kusaka, S., Geissler, F., et al. (2000). Human allograft acceptance is associated with immune regulation. J. Clin. Invest. 106, 145-155.
86. Vasiljeva, O., Papazoglou, A., Kruger, A., Brodoefel, H., Korovin, M., Deussing, J., et al. (2006). Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Res. 66, 5242-5250.
87. Vence, L., Palucka, A. K., Fay, J. W., Ito, T., Liu, Y. J., Banchereau, J., et al. (2007). Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma. Proc. Natl. Acad. Sci. U.S.A. 104, 20884-20889.
88. Vergati, M., Cereda, V., Madan, R. A., Gulley, J. L., Huen, N. Y., Rogers, C. J., et al. (2011). Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre-versus post-vaccination. Cancer Immunol. Immunother. 60, 197-206.
89. Vignali, D. A., Collison, L. W., and Workman, C. J. (2008). How regulatory T cells work. Nat. Rev. Immunol. 8, 523-532.
90. von Herrath, M. G., and Harrison, L. C. (2003). Antigen-induced regulatory T cells in autoimmunity. Nat. Rev. Immunol. 3, 223-232.
91. Wang, H. Y., Lee, D. A., Peng, G., Guo, Z., Li, Y., Kiniwa, Y., et al. (2004). Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity 20, 107-118.
92. Wang, H. Y., Peng, G., Guo, Z., Shevach, E. M., and Wang, R. F. (2005). Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells. J. Immunol. 174, 2661-2670.
93. Wang, Z., Liu, J. Q., Liu, Z., Shen, R., Zhang, G., Xu, J., et al. (2013). Tumor-derived IL-35 promotes tumor growth by enhancing myeloid cell accumulation and angiogenesis. J. Immunol. 190, 2415-2423.
94. Wei, S., Kryczek, I., Zou, L., Daniel, B., Cheng, P., Mottram, P., et al. (2005). Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma. Cancer Res. 65, 5020-5026.
95. Weiner, H. L. (2001). Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol. Rev. 182, 207-214.
96. Welters, M. J., Kenter, G. G., Piersma, S. J., Vloon, A. P., Lowik, M. J., Berends-Van Der Meer, D. M., et al. (2008). Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clin. Cancer Res. 14, 178-187.
97. Wieczorek, G., Asemissen, A., Model, F., Turbachova, I., Floess, S., Liebenberg, V., et al. (2009). Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue. Cancer Res. 69, 599-608.
98. Wolf, D., Wolf, A. M., Rumpold, H., Fiegl, H., Zeimet, A. G., Muller-Holzner, E., et al. (2005). The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin. Cancer Res. 11, 8326-8331.
99. Woo, E. Y., Chu, C. S., Goletz, T. J., Schlienger, K., Yeh, H., Coukos, G., et al. (2001). Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res. 61, 4766-4772.
100. Woo, E. Y., Yeh, H., Chu, C. S., Schlienger, K., Carroll, R. G., Riley, J. L., et al. (2002). Cutting edge: regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J. Immunol. 168, 4272-4276.
101. Yang, R., Cai, Z., Zhang, Y., Yutzy, W. H. T., Roby, K. F., and Roden, R. B. (2006). CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b+ myeloid cells. Cancer Res. 66, 6807-6815.