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References
Ambrosino, E., Spadaro, M., Iezzi, M., Curcio, C., Forni, G., Musiani, P., Wei, W. Z., and Cavallo, F. (2006). Immunosurveillance of Erbb2 carcinogenesis in transgenic mice is concealed by a dominant regulatory T-cell self-tolerance. Cancer Res 66(15):7734–7740.
Antony, P. A., Piccirillo, C. A., Akpinarli, A., Finkelstein, S. E., Speiss, P. J., Surman, D. R., Palmer, D. C., Chan, C. C., Klebanoff, C. A., Overwijk, W. W., Rosenberg, S. A., and Restifo, N. P. (2005). CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J Immunol 174(5):2591–2601.
Antony, P. A., and Restifo, N. P. (2005). CD4+CD25+ T regulatory cells, immunotherapy of cancer, and interleukin-2. J Immunother (1997) 28(2):120–128.
Attia, P., Maker, A. V., Haworth, L. R., Rogers-Freezer, L., and Rosenberg, S. A. (2005). Inability of a fusion protein of IL-2 and diphtheria toxin (Denileukin Diftitox, DAB389IL-2, ONTAK) to eliminate regulatory T lymphocytes in patients with melanoma. J Immunother (1997) 28(6):582–592.
Attia, P., Powell, D. J., Jr, Maker, A. V., Kreitman, R. J., Pastan, I., and Rosenberg, S. A. (2006). Selective elimination of human regulatory T lymphocytes in vitro with the recombinant immunotoxin LMB-2. J Immunother (1997) 29(2):208–214.
Banerjee, D. K., Dhodapkar, M. V., Matayeva, E., Steinman, R. M., and Dhodapkar, K. M. (2006). Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients. Blood 108(8):2655–2661.
Bansal-Pakala, P., Jember, A. G., and Croft, M. (2001). Signaling through OX40 (CD134) breaks peripheral T-cell tolerance. Nat Med 7(8):907–912.
Barnett, B., Kryczek, I., Cheng, P., Zou, W., and Curiel, T. J. (2005). Regulatory T cells in ovarian cancer: biology and therapeutic potential. Am J Reprod Immunol 54(6):369–377.
Berendt, M. J., and North, R. J. (1980). T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor. J Exp Med 151(1):69–80.
Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T. B., Oukka, M., Weiner, H. L., and Kuchroo, V. K. (2006). Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441(7090):235–238.
Blansfield, J. A., Beck, K. E., Tran, K., Yang, J. C., Hughes, M. S., Kammula, U. S., Royal, R. E., Topalian, S. L., Haworth, L. R., Levy, C., Rosenberg, S. A., and Sherry, R. M. (2005). Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J Immunother (1997) 28(6): 593–598.
Bui, J. D., Uppaluri, R., Hsieh, C. S., and Schreiber, R. D. (2006). Comparative analysis of regulatory and effector T cells in progressively growing versus rejecting tumors of similar origins. Cancer Res 66(14):7301–7309.
Carreras, J., Lopez-Guillermo, A., Fox, B. C., Colomo, L., Martinez, A., Roncador, G., Montserrat, E., Campo, E., and Banham, A. H. (2006). High numbers of tumor-infiltrating FOXP3-positive regulatory T cells are associated with improved overall survival in follicular lymphoma. Blood 108(9):2957–2964.
Casares, N., Arribillaga, L., Sarobe, P., Dotor, J., Lopez-Diaz de Cerio, A., Melero, I., Prieto, J., Borras-Cuesta, F., and Lasarte, J. J. (2003). CD4+/CD25+ regulatory cells inhibit activation of tumor-primed CD4+ T cells with IFN-gamma-dependent antiangiogenic activity, as well as long-lasting tumor immunity elicited by peptide vaccination. J Immunol 171(11):5931–5939.
Chen, M. L., Pittet, M. J., Gorelik, L., Flavell, R. A., Weissleder, R., von Boehmer, H., and Khazaie, K. (2005). Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc Natl Acad Sci USA 102(2):419–424.
Chen, W., Jin, W., Hardegen, N., Lei, K. J., Li, L., Marinos, N., McGrady, G., and Wahl, S. M. (2003). Conversion of peripheral CD4+CD25– naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198(12): 1875–1886.
Chiodoni, C., Iezzi, M., Guiducci, C., Sangaletti, S., Alessandrini, I., Ratti, C., Tiboni, F., Musiani, P., Granger, D. N., and Colombo, M. P. (2006). Triggering CD40 on endothelial cells contributes to tumor growth. J Exp Med 203(11):2441–2450.
Cohen, A. D., Diab, A., Perales, M. A., Wolchok, J. D., Rizzuto, G., Merghoub, T., Huggins, D., Liu, C., Turk, M. J., Restifo, N. P., Sakaguchi, S., and Houghton, A. N. (2006). Agonist anti-GITR antibody enhances vaccine-induced CD8(+) T-cell responses and tumor immunity. Cancer Res 66(9):4904–4912.
Cuenca, A., Cheng, F., Wang, H., Brayer, J., Horna, P., Gu, L., Bien, H., Borrello, I. M., Levitsky, H. I., and Sotomayor, E. M. (2003). Extra-lymphatic solid tumor growth is not immunologically ignored and results in early induction of antigen-specific T-cell anergy: dominant role of cross-tolerance to tumor antigens. Cancer Res 63(24):9007–9015.
Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., Evdemon-Hogan, M., Conejo-Garcia, J. R., Zhang, L., Burow, M., Zhu, Y., Wei, S., Kryczek, I., Daniel, B., Gordon, A., Myers, L., Lackner, A., Disis, M. L., Knutson, K. L., Chen, L., and Zou, W. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10(9):942–949.
Curti, A., Pandolfi, S., Valzasina, B., Aluigi, M., Isidori, A., Ferri, E., Salvestrini, V., Bonanno, G., Rutella, S., Durelli, I., Horenstein, A. L., Fiore, F., Massaia, M., Colombo, M. P., Baccarani, M., and Lemoli, R. M. (2007). Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25– into CD25+ T regulatory cells. Blood 109(7): 2871–2877.
Dannull, J., Su, Z., Rizzieri, D., Yang, B. K., Coleman, D., Yancey, D., Zhang, A., Dahm, P., Chao, N., Gilboa, E., and Vieweg, J. (2005). Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest 115(12):3623–3633.
Dercamp, C., Chemin, K., Caux, C., Trinchieri, G., and Vicari, A. P. (2005). Distinct and overlapping roles of interleukin-10 and CD25+ regulatory T cells in the inhibition of antitumor CD8 T-cell responses. Cancer Res 65(18):8479–8486.
Erdman, S. E., Rao, V. P., Poutahidis, T., Ihrig, M. M., Ge, Z., Feng, Y., Tomczak, M., Rogers, A. B., Horwitz, B. H., and Fox, J. G. (2003). CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res 63(18):6042–6050.
Fallarino, F., Grohmann, U., Hwang, K. W., Orabona, C., Vacca, C., Bianchi, R., Belladonna, M. L., Fioretti, M. C., Alegre, M. L., and Puccetti, P. (2003). Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 4(12):1206–1212.
Fallarino, F., Grohmann, U., You, S., McGrath, B. C., Cavener, D. R., Vacca, C., Orabona, C., Bianchi, R., Belladonna, M. L., Volpi, C., Santamaria, P., Fioretti, M. C., and Puccetti, P. (2006). The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 176(11):6752–6761.
Fontenot, J. D., Gavin, M. A., and Rudensky, A. Y. (2003). Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4(4):330–336.
Gabrilovich, D. I., Bronte, V., Chen, S. H., Colombo, M. P., Ochoa, A., Ostrand-Rosenberg, S., and Schreiber, H. (2007). The terminology issue for myeloid-derived suppressor cells. Cancer Res 67(1):425; author reply 426.
Gavin, M. A., Clarke, S. R., Negrou, E., Gallegos, A., and Rudensky, A. (2002). Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nat Immunol 3(1):33–41.
Gavin, M. A., Rasmussen, J. P., Fontenot, J. D., Vasta, V., Manganiello, V. C., Beavo, J. A., and Rudensky, A. Y. (2007). Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445(7129):771–775.
Ghiringhelli, F., Menard, C., Puig, P. E., Ladoire, S., Roux, S., Martin, F., Solary, E., Le Cesne, A., Zitvogel, L., and Chauffert, B. (2007). Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 56(5):641–648.
Ghiringhelli, F., Menard, C., Terme, M., Flament, C., Taieb, J., Chaput, N., Puig, P. E., Novault, S., Escudier, B., Vivier, E., Lecesne, A., Robert, C., Blay, J. Y., Bernard, J., Caillat-Zucman, S., Freitas, A., Tursz, T., Wagner-Ballon, O., Capron, C., Vainchencker, W., Martin, F., and Zitvogel, L. (2005a). CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med 202(8): 1075–1085.
Ghiringhelli, F., Puig, P. E., Roux, S., Parcellier, A., Schmitt, E., Solary, E., Kroemer, G., Martin, F., Chauffert, B., and Zitvogel, L. (2005b). Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing CD4+CD25+ regulatory T cell proliferation. J Exp Med 202(7):919–929.
Goldstein, I., Ben-Horin, S., Koltakov, A., Chermoshnuk, H., Polevoy, V., Berkun, Y., Amariglio, N., and Bank, I. (2007). alpha1beta1 Integrin+ and regulatory Foxp3+ T cells constitute two functionally distinct human CD4+ T cell subsets oppositely modulated by TNFalpha blockade. J Immunol 178(1):201–210.
Golgher, D., Jones, E., Powrie, F., Elliott, T., and Gallimore, A. (2002). Depletion of CD25+ regulatory cells uncovers immune responses to shared murine tumor rejection antigens. Eur J Immunol 32(11):3267–3275.
Gri, G., Gallo, E., Di Carlo, E., Musiani, P., and Colombo, M. P. (2003). OX40 ligand-transduced tumor cell vaccine synergizes with GM-CSF and requires CD40-Apc signaling to boost the host T cell antitumor response. J Immunol 170(1):99–106.
Guiducci, C., Valzasina, B., Dislich, H., and Colombo, M. P. (2005). CD40/CD40L interaction regulates CD4+CD25+ T reg homeostasis through dendritic cell-produced IL-2. Eur J Immunol 35(2):557–567.
Hiura, T., Kagamu, H., Miura, S., Ishida, A., Tanaka, H., Tanaka, J., Gejyo, F., and Yoshizawa, H. (2005). Both regulatory T cells and antitumor effector T cells are primed in the same draining lymph nodes during tumor progression. J Immunol 175(8):5058–5066.
Hodi, F. S., Mihm, M. C., Soiffer, R. J., Haluska, F. G., Butler, M., Seiden, M. V., Davis, T., Henry-Spires, R., MacRae, S., Willman, A., Padera, R., Jaklitsch, M. T., Shankar, S., Chen, T. C., Korman, A., Allison, J. P., and Dranoff, G. (2003). Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci USA 100(8):4712–4717.
Hori, S., Nomura, T., and Sakaguchi, S. (2003). Control of regulatory T cell development by the transcription factor Foxp3. Science 299(5609):1057–1061.
Hsieh, C. S., Liang, Y., Tyznik, A. J., Self, S. G., Liggitt, D., and Rudensky, A. Y. (2004). Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors. Immunity 21(2):267–277.
Hsieh, C. S., Zheng, Y., Liang, Y., Fontenot, J. D., and Rudensky, A. Y. (2006). An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat Immunol 7(4):401–410.
Huang, B., Pan, P. Y., Li, Q., Sato, A. I., Levy, D. E., Bromberg, J., Divino, C. M., and Chen, S. H. (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(2):1123–1131.
Ishida, T., Ishii, T., Inagaki, A., Yano, H., Komatsu, H., Iida, S., Inagaki, H., and Ueda, R. (2006). Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res 66(11):5716–5722.
Itoh, M., Takahashi, T., Sakaguchi, N., Kuniyasu, Y., Shimizu, J., Otsuka, F., and Sakaguchi, S. (1999). Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol 162(9):5317–5326.
Jarnicki, A. G., Lysaght, J., Todryk, S., and Mills, K. H. (2006). Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells. J Immunol 177(2):896–904.
Jones, E., Dahm-Vicker, M., Simon, A. K., Green, A., Powrie, F., Cerundolo, V., and Gallimore, A. (2002). Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immun 2:1.
Kjaergaard, J., Tanaka, J., Kim, J. A., Rothchild, K., Weinberg, A., and Shu, S. (2000). Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth. Cancer Res 60(19):5514–5521.
Ko, K., Yamazaki, S., Nakamura, K., Nishioka, T., Hirota, K., Yamaguchi, T., Shimizu, J., Nomura, T., Chiba, T., and Sakaguchi, S. (2005). Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J Exp Med 202(7):885–891.
Kohm, A. P., McMahon, J. S., Podojil, J. R., Begolka, W. S., DeGutes, M., Kasprowicz, D. J., Ziegler, S. F., and Miller, S. D. (2006). Cutting edge: anti-CD25 monoclonal antibody injection results in the functional inactivation, not depletion, of CD4+CD25+ T regulatory cells. J Immunol 176(6):3301–3305.
Kortylewski, M., Kujawski, M., Wang, T., Wei, S., Zhang, S., Pilon-Thomas, S., Niu, G., Kay, H., Mule, J., Kerr, W. G., Jove, R., Pardoll, D., and Yu, H. (2005). Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med 11(12):1314–1321.
Kretschmer, K., Apostolou, I., Hawiger, D., Khazaie, K., Nussenzweig, M. C., and von Boehmer, H. (2005). Inducing and expanding regulatory T cell populations by foreign antigen. Nat Immunol 6(12):1219–1227.
Kurooka, M., and Kaneda, Y. (2007). Inactivated Sendai virus particles eradicate tumors by inducing immune responses through blocking regulatory T cells. Cancer Res 67(1): 227–236.
Lahl, K., Loddenkemper, C., Drouin, C., Freyer, J., Arnason, J., Eberl, G., Hamann, A., Wagner, H., Huehn, J., and Sparwasser, T. (2007). Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J Exp Med 204(1):57–63.
Larmonier, N., Marron, M., Zeng, Y., Cantrell, J., Romanoski, A., Sepassi, M., Thompson, S., Chen, X., Andreansky, S., and Katsanis, E. (2007). Tumor-derived CD4(+)CD25(+) regulatory T cell suppression of dendritic cell function involves TGF-beta and IL-10. Cancer Immunol Immunother 56(1):48–59.
LeMaoult, J., Caumartin, J., Daouya, M., Favier, B., Le Rond, S., Gonzalez, A., and Carosella, E. D. (2007). Immune regulation by pretenders: cell-to-cell transfers of HLA-G make effector T cells act as regulatory cells. Blood 109(5):2040–2048.
Lin, H. H., Faunce, D. E., Stacey, M., Terajewicz, A., Nakamura, T., Zhang-Hoover, J., Kerley, M., Mucenski, M. L., Gordon, S., and Stein-Streilein, J. (2005). The macrophage F4/80 receptor is required for the induction of antigen-specific efferent regulatory T cells in peripheral tolerance. J Exp Med 201(10):1615–1625.
Liu, V. C., Wong, L. Y., Jang, T., Shah, A. H., Park, I., Yang, X., Zhang, Q., Lonning, S., Teicher, B. A., and Lee, C. (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(5):2883–2892.
Liyanage, U. K., Moore, T. T., Joo, H. G., Tanaka, Y., Herrmann, V., Doherty, G., Drebin, J. A., Strasberg, S. M., Eberlein, T. J., Goedegebuure, P. S., and Linehan, D. C. (2002). Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 169(5):2756–2761.
Lutz, M. B., and Schuler, G. (2002). Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol 23(9):445–449.
Mahnke, K., Schonfeld, K., Fondel, S., Ring, S., Karakhanova, S., Wiedemeyer, K., Bedke, T., Johnson, T. S., Storn, V., Schallenberg, S., and Enk, A. H. (2007). Depletion of CD4+CD25+ human regulatory T cells in vivo: kinetics of Treg depletion and alterations in immune functions in vivo and in vitro. Int J Cancer 120(12):2723–2733.
Malek, T. R., and Bayer, A. L. (2004). Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol 4(9):665–674.
Mallett, S., Fossum, S., and Barclay, A. N. (1990). Characterization of the MRC OX40 antigen of activated CD4 positive T lymphocytes—a molecule related to nerve growth factor receptor. EMBO J 9(4):1063–1068.
Melani, C., Chiodoni, C., Forni, G., and Colombo, M. P. (2003). Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivity. Blood 102(6):2138–2145.
Mempel, T. R., Pittet, M. J., Khazaie, K., Weninger, W., Weissleder, R., von Boehmer, H., and von Andrian, U. H. (2006). Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity 25(1):129–141.
Munn, D. H., and Mellor, A. L. (2006). The tumor-draining lymph node as an immune-privileged site. Immunol Rev 213:146–158.
Nadkarni, S., Mauri, C., and Ehrenstein, M. R. (2007). Anti-TNF-alpha therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-beta. J Exp Med 204(1):33–39.
Nair, S., Boczkowski, D., Fassnacht, M., Pisetsky, D., and Gilboa, E. (2007). Vaccination against the forkhead family transcription factor Foxp3 enhances tumor immunity. Cancer Res 67(1):371–380.
Nishikawa, H., Kato, T., Tanida, K., Hiasa, A., Tawara, I., Ikeda, H., Ikarashi, Y., Wakasugi, H., Kronenberg, M., Nakayama, T., Taniguchi, M., Kuribayashi, K., Old, L. J., and Shiku, H. (2003). CD4+ CD25+ T cells responding to serologically defined autoantigens suppress antitumor immune responses. Proc Natl Acad Sci USA 100(19):10902–10906.
Nocentini, G., Giunchi, L., Ronchetti, S., Krausz, L. T., Bartoli, A., Moraca, R., Migliorati, G., and Riccardi, C. (1997). A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis. Proc Natl Acad Sci USA 94(12): 6216–6221.
North, R. J., and Awwad, M. (1990). Elimination of cycling CD4+ suppressor T cells with an anti-mitotic drug releases non-cycling CD8+ T cells to cause regression of an advanced lymphoma. Immunology 71(1):90–95.
Onizuka, S., Tawara, I., Shimizu, J., Sakaguchi, S., Fujita, T., and Nakayama, E. (1999). Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 59(13):3128–3133.
Ormandy, L. A., Hillemann, T., Wedemeyer, H., Manns, M. P., Greten, T. F., and Korangy, F. (2005). Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res 65(6):2457–2464.
Pasare, C., and Medzhitov, R. (2003). Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science 299(5609):1033–1036.
Peng, G., Guo, Z., Kiniwa, Y., Voo, K. S., Peng, W., Fu, T., Wang, D. Y., Li, Y., Wang, H. Y., and Wang, R. F. (2005). Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function. Science 309(5739):1380–1384.
Phan, G. Q., Yang, J. C., Sherry, R. M., Hwu, P., Topalian, S. L., Schwartzentruber, D. J., Restifo, N. P., Haworth, L. R., Seipp, C. A., Freezer, L. J., Morton, K. E., Mavroukakis, S. A., Duray, P. H., Steinberg, S. M., Allison, J. P., Davis, T. A., and Rosenberg, S. A. (2003). Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci USA 100(14):8372–8377.
Powrie, F., and Mason, D. (1990). OX-22high CD4+ T cells induce wasting disease with multiple organ pathology: prevention by the OX-22low subset. J Exp Med 172(6):1701–1708.
Proietti, E., Greco, G., Garrone, B., Baccarini, S., Mauri, C., Venditti, M., Carlei, D., and Belardelli, F. (1998). Importance of cyclophosphamide-induced bystander effect on T cells for a successful tumor eradication in response to adoptive immunotherapy in mice. J Clin Invest 101(2):429–441.
Qiao, M., Thornton, A. M., and Shevach, E. M. (2007). CD4+ CD25+ [corrected] regulatory T cells render naive CD4+ CD25– T cells anergic and suppressive. Immunology 120(4):447–455.
Quezada, S. A., Peggs, K. S., Curran, M. A., and Allison, J. P. (2006). CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J Clin Invest 116(7):1935–1945.
Ramirez-Montagut, T., Chow, A., Hirschhorn-Cymerman, D., Terwey, T. H., Kochman, A. A., Lu, S., Miles, R. C., Sakaguchi, S., Houghton, A. N., and van den Brink, M. R. (2006). Glucocorticoid-induced TNF receptor family related gene activation overcomes tolerance/ignorance to melanoma differentiation antigens and enhances antitumor immunity. J Immunol 176(11):6434–6442.
Read, S., Greenwald, R., Izcue, A., Robinson, N., Mandelbrot, D., Francisco, L., Sharpe, A. H., and Powrie, F. (2006). Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo. J Immunol 177(7):4376–4383.
Reilly, R. T., Machiels, J. P., Emens, L. A., Ercolini, A. M., Okoye, F. I., Lei, R. Y., Weintraub, D., and Jaffee, E. M. (2001). The collaboration of both humoral and cellular HER-2/neu-targeted immune responses is required for the complete eradication of HER-2/neu-expressing tumors. Cancer Res 61(3):880–883.
Rolla, S., Nicolo, C., Malinarich, S., Orsini, M., Forni, G., Cavallo, F., and Ria, F. (2006). Distinct and non-overlapping T cell receptor repertoires expanded by DNA vaccination in wild-type and HER-2 transgenic BALB/c mice. J Immunol 177(11):7626–7633.
Sakaguchi, S., Fukuma, K., Kuribayashi, K., and Masuda, T. (1985). Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease. J Exp Med 161(1):72–87.
Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M., and Toda, M. (1995). Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155(3):1151–1164.
Sasada, T., Kimura, M., Yoshida, Y., Kanai, M., and Takabayashi, A. (2003). CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer 98(5):1089–1099.
Serra, P., Amrani, A., Yamanouchi, J., Han, B., Thiessen, S., Utsugi, T., Verdaguer, J., and Santamaria, P. (2003). CD40 ligation releases immature dendritic cells from the control of regulatory CD4+CD25+ T cells. Immunity 19(6):877–889.
Sharma, S., Yang, S. C., Zhu, L., Reckamp, K., Gardner, B., Baratelli, F., Huang, M., Batra, R. K., and Dubinett, S. M. (2005). Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer. Cancer Res 65(12):5211–5220.
Shevach, E. M. (2002). CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 2(6):389–400.
Shimizu, J., Yamazaki, S., and Sakaguchi, S. (1999). Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol 163(10):5211–5218.
Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y., and Sakaguchi, S. (2002). Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 3(2):135–142.
Siegmund, K., Feuerer, M., Siewert, C., Ghani, S., Haubold, U., Dankof, A., Krenn, V., Schon, M. P., Scheffold, A., Lowe, J. B., Hamann, A., Syrbe, U., and Huehn, J. (2005). Migration matters: regulatory T-cell compartmentalization determines suppressive activity in vivo. Blood 106(9):3097–3104.
Simon, A. K., Jones, E., Richards, H., Wright, K., Betts, G., Godkin, A., Screaton, G., and Gallimore, A. (2007). Regulatory T cells inhibit Fas ligand-induced innate and adaptive tumour immunity. Eur J Immunol 37(3):758–767.
Somasundaram, R., Jacob, L., Swoboda, R., Caputo, L., Song, H., Basak, S., Monos, D., Peritt, D., Marincola, F., Cai, D., Birebent, B., Bloome, E., Kim, J., Berencsi, K., Mastrangelo, M., and Herlyn, D. (2002). Inhibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+ regulatory T cells in a colorectal carcinoma patient is mediated by transforming growth factor-beta. Cancer Res 62(18):5267–5272.
Sugihara, S., Izumi, Y., Yoshioka, T., Yagi, H., Tsujimura, T., Tarutani, O., Kohno, Y., Murakami, S., Hamaoka, T., and Fujiwara, H. (1988). Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. I. Requirement of Lyt-1 dull L3T4 bright normal T cells for the induction of thyroiditis. J Immunol 141(1):105–113.
Sutmuller, R. P., van Duivenvoorde, L. M., van Elsas, A., Schumacher, T. N., Wildenberg, M. E., Allison, J. P., Toes, R. E., Offringa, R., and Melief, C. J. (2001). Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J Exp Med 194(6):823–832.
Tadokoro, C. E., Shakhar, G., Shen, S., Ding, Y., Lino, A. C., Maraver, A., Lafaille, J. J., and Dustin, M. L. (2006). Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J Exp Med 203(3):505–511.
Taguchi, O., and Takahashi, T. (1996). Administration of anti-interleukin-2 receptor alpha antibody in vivo induces localized autoimmune disease. Eur J Immunol 26(7):1608–1612.
Takahashi, T., Kuniyasu, Y., Toda, M., Sakaguchi, N., Itoh, M., Iwata, M., Shimizu, J., and Sakaguchi, S. (1998). Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol 10(12):1969–1980.
Takeda, I., Ine, S., Killeen, N., Ndhlovu, L. C., Murata, K., Satomi, S., Sugamura, K., and Ishii, N. (2004). Distinct roles for the OX40–OX40 ligand interaction in regulatory and nonregulatory T cells. J Immunol 172(6):3580–3589.
Tang, Q., Adams, J. Y., Tooley, A. J., Bi, M., Fife, B. T., Serra, P., Santamaria, P., Locksley, R. M., Krummel, M. F., and Bluestone, J. A. (2006). Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice. Nat Immunol 7(1):83–92.
Tang, Q., Henriksen, K. J., Boden, E. K., Tooley, A. J., Ye, J., Subudhi, S. K., Zheng, X. X., Strom, T. B., and Bluestone, J. A. (2003). Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J Immunol 171(7):3348–3352.
Tang, Q., and Krummel, M. F. (2006). Imaging the function of regulatory T cells in vivo. Curr Opin Immunol 18(4):496–502.
Thomas, D. A., and Massague, J. (2005). TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell 8(5):369–380.
Thornton, A. M., and Shevach, E. M. (1998). CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 188(2):287–296.
Turk, M. J., Guevara-Patino, J. A., Rizzuto, G. A., Engelhorn, M. E., Sakaguchi, S., and Houghton, A. N. (2004). Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells. J Exp Med 200(6):771–782.
Valzasina, B., Guiducci, C., Dislich, H., Killeen, N., Weinberg, A. D., and Colombo, M. P. (2005). Triggering of OX40 (CD134) on CD4(+)CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR. Blood 105(7): 2845–2851.
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(8):4488–4495.
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., and Stockinger, B. (2006). TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24(2):179–189.
Vlad, G., Cortesini, R., and Suciu-Foca, N. (2005). License to heal: bidirectional interaction of antigen-specific regulatory T cells and tolerogenic APC. J Immunol 174(10):5907–5914.
Wang, H. Y., Lee, D. A., Peng, G., Guo, Z., Li, Y., Kiniwa, Y., Shevach, E. M., and Wang, R. F. (2004). Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity 20(1):107–118.
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(5):2661–2670.
Wang, J., Ioan-Facsinay, A., van der Voort, E. I., Huizinga, T. W., and Toes, R. E. (2007). Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur J Immunol 37(1):129–138.
Weinberg, A. D., Rivera, M. M., Prell, R., Morris, A., Ramstad, T., Vetto, J. T., Urba, W. J., Alvord, G., Bunce, C., and Shields, J. (2000). Engagement of the OX-40 receptor in vivo enhances antitumor immunity. J Immunol 164(4):2160–2169.
Williams, L. M., and Rudensky, A. Y. (2007). Maintenance of the Foxp3-dependent developmental program in mature regulatory T cells requires continued expression of Foxp3. Nat Immunol 8(3):277–284.
Wing, K., Fehervari, Z., and Sakaguchi, S. (2006). Emerging possibilities in the development and function of regulatory T cells. Int Immunol 18(7):991–1000.
Wing, K., and Sakaguchi, S. (2006). Regulatory T cells as potential immunotherapy in allergy. Curr Opin Allergy Clin Immunol 6(6):482–488.
Woo, E. Y., Chu, C. S., Goletz, T. J., Schlienger, K., Yeh, H., Coukos, G., Rubin, S. C., Kaiser, L. R., and June, C. H. (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(12):4766–4772.
Yamazaki, S., Iyoda, T., Tarbell, K., Olson, K., Velinzon, K., Inaba, K., and Steinman, R. M. (2003). Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells. J Exp Med 198(2):235–247.
Yang, Z. Z., Novak, A. J., Stenson, M. J., Witzig, T. E., and Ansell, S. M. (2006). Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma. Blood 107(9):3639–3646.
Yu, P., Lee, Y., Liu, W., Krausz, T., Chong, A., Schreiber, H., and Fu, Y. X. (2005). Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med 201(5):779–791.
Zhao, D. M., Thornton, A. M., DiPaolo, R. J., and Shevach, E. M. (2006). Activated CD4+CD25+ T cells selectively kill B lymphocytes. Blood 107(10):3925–3932.
Zhou, G., Drake, C. G., and Levitsky, H. I. (2006). Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood 107(2):628–636.
Zhou, G., and Levitsky, H. I. (2007). Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance. J Immunol 178(4):2155–2162.
Zitvogel, L., Tesniere, A., and Kroemer, G. (2006). Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 6(10):715–727.
Zou, W. (2006). Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6(4):295–307.
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Piconese, S., Colombo, M.P. (2008). Regulatory T Cells in Cancer. In: Gabrilovich, D.I., Hurwitz, A.A. (eds) Tumor-Induced Immune Suppression. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69118-3_4
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