Ontogeny of Tumor-associated CD4+CD25+Foxp3+ T-regulatory Cells

References

• Adeegbe DO, Nishikawa H. (2013). Natural and induced T regulatory cells in cancer. Front Immunol, 4, 190. doi: 10.3389/fimmu.2013.00190.
   PubMed Web of Science ®Google Scholar
• Akimova T, Beier UH, Wang L, et al. (2011). Helios expression is a marker of T cell activation and proliferation. PLoS One, 6(8), e24226. doi: 10.1371/journal.pone.0024226.
   PubMedGoogle Scholar
• Ali K, Soond DR, Pineiro R, et al. (2014). Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature 510(7505), 407–411. doi: 10.1038/nature13444.
   PubMed Web of Science ®Google Scholar
• Arpaia NC, Campbell X, Fan S, et al. (2013). Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature, 504(7480), 451–455. doi: 10.1038/nature12726.
   PubMed Web of Science ®Google Scholar
• Awwad M, North RJ. (1988). Immunologically mediated regression of a murine lymphoma after treatment with anti-L3T4 antibody. A consequence of removing L3T4+ suppressor T cells from a host generating predominantly Lyt-2+ T cell-mediated immunity. J Exp Med, 168(6), 2193–2206.
   Google Scholar
• Awwad M, North RJ. (1989). Cyclophosphamide-induced immunologically mediated regression of a cyclophosphamide-resistant murine tumor: a consequence of eliminating precursor L3T4+ suppressor T-cells. Cancer Res, 49(7), 1649–1654.
   PubMed Web of Science ®Google Scholar
• Baur AS, Lutz MB, Schierer S, et al. (2013). Denileukin diftitox (ONTAK) induces a tolerogenic phenotype in dendritic cells and stimulates survival of resting Treg. Blood, 122(13), 2185–2194. doi: 10.1182/blood-2012-09-456988.
   PubMed Web of Science ®Google Scholar
• Benacerraf B, Germain RN. (1981). A single major pathway of T-lymphocyte interactions in antigen-specific immune suppression. Scand J Immunol, 13(1), 1–10.
   Google Scholar
• Berendt MJ, North RJ. (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.
   Google Scholar
• Bergot AS, Chaara W, Ruggiero E, et al. (2015). TCR sequences and tissue distribution discriminate the subsets of naive and activated/memory Treg cells in mice. Eur J Immunol, 45(5), 1524–1534. doi: 10.1002/eji.201445269.
   PubMed Web of Science ®Google Scholar
• Blatner NR, Gounari F, Khazaie K. (2013). The two faces of regulatory T cells in cancer. Oncoimmunology, 2(5), e23852. doi: 10.4161/onci.23852.
   PubMed Web of Science ®Google Scholar
• Blatner NR, Mulcahy MF, Dennis KL, et al. (2012). Expression of RORgammat marks a pathogenic regulatory T cell subset in human colon cancer. Sci Transl Med, 4(164), 164ra159. doi: 10.1126/scitranslmed.3004566.
   PubMed Web of Science ®Google Scholar
• Bulliard Y, Jolicoeur R, Zhang J, et al. (2014). OX40 engagement depletes intratumoral Tregs via activating FcgammaRs, leading to antitumor efficacy. Immunol Cell Biol, 92(6), 475–480. doi: 10.1038/icb.2014.26.
   PubMed Web of Science ®Google Scholar
• Cabrera R, Ararat M, Xu Y, et al. (2013). Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma. Cancer Immunol Immunother, 62(4), 737–746. doi: 10.1007/s00262-012-1380-8.
   PubMed Web of Science ®Google Scholar
• Cantor H, Hugenberger J, McVay-Boudreau L, et al. (1978). Immunoregulatory circuits among T-cell sets. Identification of a subpopulation of T-helper cells that induces feedback inhibition. J Exp Med, 148(4), 871–877.
   Google Scholar
• Cantor H, Shen FW, Boyse EA. (1976). Separation of helper T cells from suppressor T cells expressing different Ly components. II. Activation by antigen: after immunization, antigen-specific suppressor and helper activities are mediated by distinct T-cell subclasses. J Exp Med, 143(6), 1382–1390.
   Google Scholar
• Chaudhry A, Rudensky AY. (2013). Control of inflammation by integration of environmental cues by regulatory T cells. J Clin Invest, 123(3), 939–944. doi: 10.1172/JCI57175.
   PubMed Web of Science ®Google Scholar
• Chen KJ, Lin SZ, Zhou L, et al. (2011). Selective recruitment of regulatory T cell through CCR6-CCL20 in hepatocellular carcinoma fosters tumor progression and predicts poor prognosis. PLoS One, 6(9), e24671. doi: 10.1371/journal.pone.0024671.
   PubMed Web of Science ®Google Scholar
• Chung AY, Li Q, Blair SJ, et al. (2014). Oral interleukin-10 alleviates polyposis via neutralization of pathogenic T-regulatory cells. Cancer Res, 74(19), 5377–5385. doi: 10.1158/0008-5472.CAN-14-0918.
   PubMed Web of Science ®Google Scholar
• Curiel TJ, Coukos G, Zou L, et al. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med, 10(9), 942–949. doi: 10.1038/nm1093.
   PubMed Web of Science ®Google Scholar
• Curti BD, Kovacsovics-Bankowski M, Morris N, et al. (2013). OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res, 73(24), 7189–7198. doi: 10.1158/0008-5472.CAN-12-4174.
   PubMed Web of Science ®Google Scholar
• Darrasse-Jeze G, Bergot AS, et al. (2009a). Tumor emergence is sensed by self-specific CD44hi memory Tregs that create a dominant tolerogenic environment for tumors in mice. J Clin Invest, 119(9), 2648–2662. doi: 10.1172/JCI36628.
   PubMed Web of Science ®Google Scholar
• Darrasse-Jeze G, Deroubaix S, Mouquet H, et al. (2009b). Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. J Exp Med, 206(9), 1853–1862. doi: 10.1084/jem.20090746.
   PubMed Web of Science ®Google Scholar
• Darrasse-Jeze, G, Podsypanina K. (2013). How numbers, nature, and immune status of foxp3(+) regulatory T-cells shape the early immunological events in tumor development. Front Immunol, 4, 292. doi: 10.3389/fimmu.2013.00292.
   PubMed Web of Science ®Google Scholar
• de Vries IJ, Castelli C, Huygens C, et al. (2011). Frequency of circulating Tregs with demethylated FOXP3 intron 1 in melanoma patients receiving tumor vaccines and potentially Treg-depleting agents. Clin Cancer Res, 17(4), 841–848. doi: 10.1158/1078-0432.CCR-10-2227.
   PubMed Web of Science ®Google Scholar
• Dye ES, North RJ. (1981). T cell-mediated immunosuppression as an obstacle to adoptive immunotherapy of the P815 mastocytoma and its metastases. J Exp Med, 154(4), 1033–1042.
   PubMed Web of Science ®Google Scholar
• Dye ES, North RJ. (1984). Specificity of the T cells that mediate and suppress adoptive immunotherapy of established tumors. J Leukoc Biol, 36(1), 27–37.
   Google Scholar
• Eardley DD, Hugenberger J, McVay-Boudreau L, et al. (1978). Immunoregulatory circuits among T-cell sets. I. T-helper cells induce other T-cell sets to exert feedback inhibition. J Exp Med, 147(4), 1106–1115.
   Google Scholar
• Elkord E, Sharma S, Burt DJ, Hawkins RE. (2011). Expanded subpopulation of FoxP3+ T regulatory cells in renal cell carcinoma co-express Helios, indicating they could be derived from natural but not induced Tregs. Clin Immunol, 140(3), 218–222. doi: 10.1016/j.clim.2011.04.014.
   PubMed Web of Science ®Google Scholar
• Facciabene A, Motz GT, Coukos G. (2012). T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res, 72(9), 2162–2171. doi: 10.1158/0008-5472.CAN-11-3687.
   PubMed Web of Science ®Google Scholar
• Facciabene A, Peng X, Hagemann IS, et al. (2011). Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature, 475(7355), 226–230. doi: 10.1038/nature10169.
   PubMed Web of Science ®Google Scholar
• Fontenot JD, Gavin MA, Rudensky AY. (2003). Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol, 4(4), 330–336. doi: 10.1038/ni904.
   PubMed Web of Science ®Google Scholar
• Fowell D, Mason D. (1993). Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+ T cell subset that inhibits this autoimmune potential. J Exp Med, 177(3), 627–636.
   Google Scholar
• Frey DM, Droeser RA, Viehl CT, et al. (2010). High frequency of tumor-infiltrating FOXP3(+) regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients. Int J Cancer, 126(11), 2635–2643. doi: 10.1002/ijc.24989.
   PubMed Web of Science ®Google Scholar
• Fridman WH, Pages F, Sautes-Fridman C, Galon J. (2012). The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer, 12(4), 298–306. doi: 10.1038/nrc3245.
   PubMed Web of Science ®Google Scholar
• Fujimoto S, Greene MI, Sehon AH. (1976a). Regualtion of the immune response to tumor antigens. I. Immunosuppressor cells in tumor-bearing hosts. J Immunol, 116(3), 791–799.
   Google Scholar
• Fujimoto S, Greene MI, Sehon AH. (1976b). Regulation of the immune response to tumor antigens. II. The nature of immunosuppressor cells in tumor-bearing hosts. J Immunol, 116(3), 800–806.
   Google Scholar
• Germain RN. (2008). Special regulatory T-cell review: A rose by any other name: from suppressor T cells to Tregs, approbation to unbridled enthusiasm. Immunology, 123(1), 20–27. doi: 10.1111/j.1365-2567.2007.02779.x.
   PubMed Web of Science ®Google Scholar
• Gershon RK, Cohen P, Hencin R, Liebhaber SA. (1972). Suppressor T cells. J Immunol, 108(3), 586–590.
   Google Scholar
• Gershon RK, Kondo K. (1970). Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology, 18(5), 723–737.
   Google Scholar
• Gershon RK, Kondo K. (1971). Infectious immunological tolerance. Immunology, 21(6), 903–914.
   Google Scholar
• Gershon RK, Mokyr MB, Mitchell MS. (1974). Activation of suppressor T cells by tumour cells and specific antibody. Nature, 250(467), 594–596.
   Google Scholar
• Getnet D, Maris CH, Hipkiss EL, et al. (2009). Tumor recognition and self-recognition induce distinct transcriptional profiles in antigen-specific CD4 T cells. J Immunol, 182(8), 4675–4685. doi: 10.4049/jimmunol.0803400.
   PubMed Web of Science ®Google Scholar
• Glaser M. (1979). Regulation of specific cell-mediated cytotoxic response against SV40-induced tumor associated antigens by depletion of suppressor T cells with cyclophosphamide in mice. J Exp Med, 149(3), 774–779.
   PubMed Web of Science ®Google Scholar
• Gobert M, Treilleux I, Bendriss-Vermare N, et al. (2009). Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer Res, 69(5), 2000–2009. doi: 10.1158/0008-5472.CAN-08-2360.
   Web of Science ®Google Scholar
• Gounaris E, Blatner NR, Dennis K, et al. (2009). T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis. Cancer Res, 69(13), 5490–5497. doi: 10.1158/0008-5472.CAN-09-0304.
   PubMed Web of Science ®Google Scholar
• Gratz IK, Campbell DJ. (2014). Organ-specific and memory treg cells: specificity, development, function, and maintenance. Front Immunol, 5, 333. doi: 10.3389/fimmu.2014.00333.
   PubMed Web of Science ®Google Scholar
• Greene MI, Fujimoto S, Sehon AH. (1977). Regulation of the immune response to tumor antigens. III. Characterization of thymic suppressor factor(s) produced by tumor-bearing hosts. J Immunol, 119(2), 757–764.
   Google Scholar
• Greene MI, Perry LL. (1978). Regulation of the immune response to tumor antigen. VI. Differential specificities of suppressor T cells or their products and effector T cells. J Immunol, 121(6), 2363–2366.
   Google Scholar
• Groux H, O’Garra A, Bigler M, et al. (1997). A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature, 389(6652), 737–742. doi: 10.1038/39614.
   PubMed Web of Science ®Google Scholar
• Gu T, Rowswell-Turner RB, Kilinc MO, Egilmez NK. (2010). Central role of IFNgamma-indoleamine 2,3-dioxygenase axis in regulation of interleukin-12-mediated antitumor immunity. Cancer Res, 70(1), 129–138. doi: 10.1158/0008-5472.CAN-09-3170.
   PubMed Web of Science ®Google Scholar
• Hansen W, Hutzler M, Abel S, et al. (2012). Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth. J Exp Med 209(11), 2001–2016. doi: 10.1084/jem.20111497.
   PubMed Web of Science ®Google Scholar
• Harden JL, Gu MO, Kilinc RB et al. (2011). Dichotomous effects of IFN-gamma on dendritic cell function determine the extent of IL-12-driven antitumor T cell immunity. J Immunol, 187(1), 126–132. doi: 10.4049/jimmunol.1100168.
   PubMed Web of Science ®Google Scholar
• Hellstrom KE, Hellstrom I, Kant JA, Tamerius JD. (1978). Regression and inhibition of sarcoma growth by interference with a radiosensitive T-cell population. Exp Med, 148(3), 799–804.
   Google Scholar
• Herzenberg LA, Okumura K, Cantor VL. (1976). T-cell regulation of antibody responses: demonstration of allotype-specific helper T cells and their specific removal by suppressor T cells. J Exp Med, 144(2), 330–344.
   Google Scholar
• Herzenberg LA, Okumura K, Metzler CM. (1975). Regulation of immunoglobulin and antibody production by allotype suppressor T cells in mice. Transplant Rev. 27, 57–83.
   PubMed Web of Science ®Google Scholar
• Hindley JP, Ferreira C, Jones E, et al. (2011). Analysis of the T-cell receptor repertoires of tumor-infiltrating conventional and regulatory T cells reveals no evidence for conversion in carcinogen-induced tumors. Cancer Res, 71(3), 736–746. doi: 10.1158/0008-5472.CAN-10-1797.
   PubMed Web of Science ®Google Scholar
• Hiura T, Kagamu H, Miura S, et al. (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.
   PubMed Web of Science ®Google Scholar
• Hori S, Nomura T, Sakaguchi S. (2003). Control of regulatory T cell development by the transcription factor Foxp3. Science 299(5609), 1057–61. doi: 10.1126/science.1079490.
   PubMed Web of Science ®Google Scholar
• Hossain DM, Panda AK, Chakrabarty S, et al. (2015). MEK inhibition prevents tumour-shed transforming growth factor-beta-induced T-regulatory cell augmentation in tumour milieu. Immunology, 144(4), 561–573. doi: 10.1111/imm.12397.
   PubMed Web of Science ®Google Scholar
• Ishida T, Ishii T, Inagaki A, et al. (2006). Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res 66(11), 5716–5722. doi: 10.1158/0008-5472.CAN-06-0261.
   Google Scholar
• Ito T, Hanabuchi S, Wang YH, et al. (2008). Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery. Immunity, 28(6), 870–880. doi: 10.1016/j.immuni.2008.03.018.
   PubMed Web of Science ®Google Scholar
• Jaafar F, Righi E, Lindstrom V, et al. (2009). Correlation of CXCL12 expression and FoxP3+ cell infiltration with human papillomavirus infection and clinicopathological progression of cervical cancer. Am J Pathol 175(4), 1525–1535. doi: 10.2353/ajpath.2009.090295.
   PubMed Web of Science ®Google Scholar
• Jacobs JF, Punt CJ, Lesterhuis RP, et al. (2010). Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I/II study in metastatic melanoma patients. Clin Cancer Res, 16(20), 5067–5078. doi: 10.1158/1078-0432.CCR-10-1757.
   PubMed Web of Science ®Google Scholar
• Jandus C, Bioley G, Dojcinovic D, et al. (2009). Tumor antigen-specific FOXP3+ CD4 T cells identified in human metastatic melanoma: peptide vaccination results in selective expansion of Th1-like counterparts. Cancer Res, 69(20), 8085–8093. doi: 10.1158/0008-5472.CAN-09-2226.
   PubMed Web of Science ®Google Scholar
• Jordan MS, Boesteanu A, Reed AJ, et al. (2001). Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol, 2(4), 301–306. doi: 10.1038/86302.
   PubMed Web of Science ®Google Scholar
• Josefowicz SZ, Lu LF, Rudensky AY. (2012). Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol, 30, 531–564. doi: 10.1146/annurev.immunol.25.022106.141623.
   PubMed Web of Science ®Google Scholar
• Khattri R, Cox T, Yasayko SA, Ramsdell F. (2003). An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol, 4(4), 337–342. doi: 10.1038/ni909.
   PubMed Web of Science ®Google Scholar
• Kim KS, Hong SW, Han D, et al. (2016). Dietary antigens limit mucosal immunity by inducing regulatory T cells in the small intestine. Science, 351(6275), 858–863. doi: 10.1126/science.aac5560.
   PubMed Web of Science ®Google Scholar
• Kobori JA, Strauss E, Minard K, Hood L. (1986). Molecular analysis of the hotspot of recombination in the murine major histocompatibility complex. Science, 234(4773), 173–179.
   Google Scholar
• Kronenberg M, Steinmetz M, Kobori J, et al. (1983). RNA transcripts for I-J polypeptides are apparently not encoded between the I-A and I-E subregions of the murine major histocompatibility complex. Proc Natl Acad Sci USA, 80(18), 5704–5708.
   Google Scholar
• Kuczma M, Kopij M, Pawlikowska I, et al. (2010). Intratumoral convergence of the TCR repertoires of effector and Foxp3+ CD4+ T cells. PLoS One, 5(10), e13623. doi: 10.1371/journal.pone.0013623.
   Google Scholar
• Kurose K, Ohue Y, Wada H, et al. (2015). Phase Ia Study of FoxP3+ CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4 Antibody, KW-0761, in Cancer Patients. Clin Cancer Res, 21(19), 4327–4336. doi: 10.1158/1078-0432.CCR-15-0357.
   PubMed Web of Science ®Google Scholar
• Lee WS, Park S, Lee WY, et al. (2010). Clinical impact of tumor-infiltrating lymphocytes for survival in stage II colon cancer. Cancer, 116(22), 5188–5199. doi: 10.1002/cncr.25293.
   PubMed Web of Science ®Google Scholar
• Li Q, Virtuoso LP, Anderson CD, Egilmez NK. (2015). Regulatory rebound in IL-12-treated tumors is driven by uncommitted peripheral regulatory T cells. J Immunol, 195(3), 1293–300. doi: 10.4049/jimmunol.1403078.
   PubMed Web of Science ®Google Scholar
• Litzinger MT, Fernando R, Curiel TJ, et al. (2007). IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity. Blood, 110(9), 3192–201. doi: 10.1182/blood-2007-06-094615.
   PubMed Web of Science ®Google Scholar
• Liu C, Workman CJ, Vignali DA. (2016). Targeting Regulatory T Cells in Tumors. FEBS J. doi: 10.1111/febs.13656.
   Google Scholar
• Liu VC, Wong LY, Jang T, 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(5), 2883–2892.
   PubMed Web of Science ®Google Scholar
• Liu W, Putnam AL, Xu-Yu Z, Szot GL, et al. (2006). CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med, 203(7), 1701–1711. doi: 10.1084/jem.20060772.
   PubMed Web of Science ®Google Scholar
• Mahalingam J, Lin CY, Chiang JM, et al. (2014). CD4(+) T cells expressing latency-associated peptide and Foxp3 are an activated subgroup of regulatory T cells enriched in patients with colorectal cancer. PLoS One, 9(9), e108554. doi: 10.1371/journal.pone.0108554.
   PubMed Web of Science ®Google Scholar
• Mahnke K, Schonfeld K, Fondel S, et al. (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. doi: 10.1002/ijc.22617.
   PubMed Web of Science ®Google Scholar
• Malchow S, Leventhal DS, Nishi S, et al. (2013). Aire-dependent thymic development of tumor-associated regulatory T cells. Science, 339(6124), 1219–1224. doi: 10.1126/science.1233913.
   PubMed Web of Science ®Google Scholar
• Malchow S, Leventhal DS, Savage PA. (2013). Organ-specific regulatory T cells of thymic origin are expanded in murine prostate tumors. Oncoimmunology, 2(7), e24898. doi: 10.4161/onci.24898.
   Google Scholar
• Manoukian G, Hagemeister F. (2009). Denileukin diftitox: a novel immunotoxin. Expert Opin Biol Ther, 9(11), 1445–1451. doi: 10.1517/14712590903348135.
   PubMed Web of Science ®Google Scholar
• McDougal JS, Shen FW, Cort SP, Bard J. (1980). Feedback suppression: phenotypes of T cell subsets involved in the Ly1 T cell-induced immunoregulatory circuit. J Immunol, 125(3), 1157–60.
   PubMed Web of Science ®Google Scholar
• Miller AM, Lundberg K, Ozenci V, et al. (2006). CD4+CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol, 177(10), 7398–7405.
   PubMed Web of Science ®Google Scholar
• Mills CD, North RJ. (1983). Expression of passively transferred immunity against an established tumor depends on generation of cytolytic T cells in recipient. Inhibition by suppressor T cells. J Exp Med, 157(5), 1448–1460.
   Google Scholar
• Milpied P, Renand A, Bruneau J, et al. (2009). Neuropilin-1 is not a marker of human Foxp3+ Treg. Eur J Immunol, 39(6), 1466–1471. doi: 10.1002/eji.200839040.
   PubMed Web of Science ®Google Scholar
• Miyara M, Yoshioka Y, Kitoh A, et al. (2009). Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity, 30(6), 899–911. doi: 10.1016/j.immuni.2009.03.019.
   PubMed Web of Science ®Google Scholar
• Mizukami Y, Kono K, Kawaguchi Y, et al. (2008). CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer. Int J Cancer, 122(10), 2286–2293. doi: 10.1002/ijc.23392.
   PubMed Web of Science ®Google Scholar
• Mucida D, Kutchukhidze N, Erazo A, et al. (2005). Oral tolerance in the absence of naturally occurring Tregs. J Clin Invest, 115(7), 1923–1933. doi: 10.1172/JCI24487.
   PubMed Web of Science ®Google Scholar
• Munn DH, Mellor AL. (2016). IDO in the Tumor microenvironment: Inflammation, counter-regulation, and tolerance. Trends Immunol 37(3), 193–207. doi: 10.1016/j.it.2016.01.002.
   Google Scholar
• Murphy DB, Herzenberg LA, Okumura K, et al. (1976). A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes. J Exp Med, 144(3), 699–712.
   PubMed Web of Science ®Google Scholar
• Nair RE, Jong YS, Jones SA, et al. (2006b). IL-12 + GM-CSF microsphere therapy induces eradication of advanced spontaneous tumors in her-2/neu transgenic mice but fails to achieve long-term cure due to the inability to maintain effector T-cell activity. J Immunother, 29(1), 10–20.
   PubMed Web of Science ®Google Scholar
• Nair RE, Kilinc MO, Jones SA, Egilmez NK. (2006a). Chronic immune therapy induces a progressive increase in intratumoral T suppressor activity and a concurrent loss of tumor-specific CD8+ T effectors in her-2/neu transgenic mice bearing advanced spontaneous tumors. J Immunol, 176(12), 7325–7334.
   PubMed Web of Science ®Google Scholar
• Nishikawa H, Sakaguchi S. (2014). Regulatory T cells in cancer immunotherapy. Curr Opin Immunol, 27, 1–7. doi: 10.1016/j.coi.2013.12.005.
   PubMed Web of Science ®Google Scholar
• North RJ. (1984). Gamma-irradiation facilitates the expression of adoptive immunity against established tumors by eliminating suppressor T cells. Cancer Immunol Immunother, 16(3), 175–181.
   Google Scholar
• North RJ, Bursuker I. (1984). Generation and decay of the immune response to a progressive fibrosarcoma. I. Ly-1+2- suppressor T cells down-regulate the generation of Ly-1-2+ effector T cells. J Exp Med, 159(5), 1295–1311.
   Google Scholar
• North RJ, Dye ES. (1985). Ly 1+2- suppressor T cells down-regulate the generation of Ly 1-2+ effector T cells during progressive growth of the P815 mastocytoma. Immunology, 54(1), 47–56.
   PubMed Web of Science ®Google Scholar
• Nosho K, Baba Y, Tanaka N, et al. (2010). Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J Pathol, 222(4), 350–366. doi: 10.1002/path.2774.
   PubMed Web of Science ®Google Scholar
• Nystrom SN, Bourges D, Garry S, et al. 2014. Transient Treg-cell depletion in adult mice results in persistent self-reactive CD4(+) T-cell responses. Eur J Immunol, 44(12), 3621–3631. doi: 10.1002/eji.201344432.
   PubMed Web of Science ®Google Scholar
• Ohnmacht C, Park JH, Cording S, et al. (2015). The microbiota regulates type 2 immunity through RORgammat(+) T cells. Science, 349(6251), 989–993. doi: 10.1126/science.aac4263.
   PubMed Web of Science ®Google Scholar
• Okumura K, Herzenberg LA, Murphy DB, et al. (1976). Selective expression of H-2 (i-region) loci controlling determinants on helper and suppressor T lymphocytes. J Exp Med, 144(3), 685–698.
   PubMed Web of Science ®Google Scholar
• Pandiyan P, Zheng L, Ishihara S, et al. (2007). CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol, 8(12), 1353–62. doi: 10.1038/ni1536.
   PubMed Web of Science ®Google Scholar
• Perry LL, Benacerraf B, Greene MI. (1978). Regulation of the immune response to tumor antigen. IV. Tumor antigen-specific suppressor factor(s) bear I-J determinants and induce suppressor T cells in vivo. J Immunol 121(6), 2144–2147.
   Google Scholar
• Perry LL, Dorf ME, Benacerraf B, Greene MI. (1979). Regulation of immune response to tumor antigen: interference with syngeneic tumor immunity by anti-IA alloantisera. Proc Natl Acad Sci USA, 76(2), 920–924.
   Google Scholar
• Perry LL, Kripke ML, Benacerraf B, et al. (1980). Regulation of the immune response to tumor antigen. VIII. The effects of host specific anti-I-J antibodies on the immune response to tumors of different origin. Cell Immunol, 51(2), 349–359.
   Google Scholar
• Powrie F, 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.
   PubMed Web of Science ®Google Scholar
• Rasku MA, Clem AL, Telang S, et al. (2008). Transient T cell depletion causes regression of melanoma metastases. J Transl Med, 6, 12. doi: 10.1186/1479-5876-6-12.
   PubMed Web of Science ®Google Scholar
• Rech AJ, Mick R, Martin S, et al. (2012). CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients. Sci Transl Med, 4(134), 134ra62. doi: 10.1126/scitranslmed.3003330.
   PubMed Web of Science ®Google Scholar
• Rollinghoff M, Starzinski-Powitz A, Pfizenmaier K, Wagner H. (1977). Cyclophosphamide-sensitive T lymphocytes suppress the in vivo generation of antigen-specific cytotoxic T lymphocytes. J Exp Med, 145(2), 455–459.
   Google Scholar
• Sainz-Perez A, Lim A, Lemercier B, Leclerc C. (2012). The T-cell receptor repertoire of tumor-infiltrating regulatory T lymphocytes is skewed toward public sequences. Cancer Res, 72(14), 3557–3569. doi: 10.1158/0008-5472.CAN-12-0277.
   PubMed Web of Science ®Google Scholar
• Sakaguchi S, Fukuma K, Kuribayashi K, 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.
   Google Scholar
• Sakaguchi S, Sakaguchi N, Asano M, et al. (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.
   Google Scholar
• Sakaguchi S, Takahashi T, Nishizuka Y. (1982). Study on cellular events in post-thymectomy autoimmune oophoritis in mice. II. Requirement of Lyt-1 cells in normal female mice for the prevention of oophoritis. J Exp Med 156(6), 1577–1586.
   Google Scholar
• Salama P, Phillips M, Grieu F, et al. (2009). Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol, 27(2), 186–192. doi: 10.1200/JCO.2008.18.7229.
   PubMed Web of Science ®Google Scholar
• Sato E, Olson SH, Ahn J, et al. (2005). Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 102(51), 18538–18543. doi: 10.1073/pnas.0509182102.
   PubMed Web of Science ®Google Scholar
• Savage PA, Leventhal DS, Malchow S. (2014). Shaping the repertoire of tumor-infiltrating effector and regulatory T cells. Immunol Rev, 259(1), 245–258. doi: 10.1111/imr.12166.
   PubMed Web of Science ®Google Scholar
• Savage PA, Malchow S, Leventhal DS. (2013). Basic principles of tumor-associated regulatory T cell biology. Trends Immunol, 34(1), 33–40. doi: 10.1016/j.it.2012.08.005.
   PubMed Web of Science ®Google Scholar
• Schaefer JT, Patterson JW, Deacon DH, et al. (2010). Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis. J Transl Med, 8, 79. doi: 10.1186/1479-5876-8-79.
   PubMed Web of Science ®Google Scholar
• Schatten S, Drebin JA, Perry LL, et al. (1984). Regulation of the immune response to tumor antigens. X. Activation of third-order suppressor T cells that abrogate anti-tumor immune responses. J Immunol, 133(2), 1064–1069.
   Google Scholar
• Schott AK, Pries R, Wollenberg B. (2010). Permanent up-regulation of regulatory T-lymphocytes in patients with head and neck cancer. Int J Mol Med, 26(1), 67–75.
   Google Scholar
• Schreiber TH, Wolf D, Bodero M, Podack E. (2012). Tumor antigen specific iTreg accumulate in the tumor microenvironment and suppress therapeutic vaccination. Oncoimmunology, 1(5), 642–648. doi: 10.4161/onci.20298.
   PubMed Web of Science ®Google Scholar
• Seddiki N, Santner-Nanan B, Martinson J, et al. (2006). Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med, 203(7), 1693–1700. doi: 10.1084/jem.20060468.
   PubMed Web of Science ®Google Scholar
• Sefik E, Geva-Zatorsky N, Oh S, et al. (2015). Individual intestinal symbionts induce a distinct population of RORgamma(+) regulatory T cells. Science, 349(6251), 993–997. doi: 10.1126/science.aaa9420.
   PubMed Web of Science ®Google Scholar
• Shevach EM, Thornton AM. (2014). tTregs, pTregs, and iTregs: similarities and differences. Immunol Rev, 259(1), 88–102. doi: 10.1111/imr.12160.
   PubMed Web of Science ®Google Scholar
• Shevchenko I, Karakhanova S, Soltek S, et al. (2013). Low-dose gemcitabine depletes regulatory T cells and improves survival in the orthotopic Panc02 model of pancreatic cancer. Int J Cancer, 133(1), 98–107. doi: 10.1002/ijc.27990.
   PubMed Web of Science ®Google Scholar
• Smigiel KS, Srivastava S, Stolley JM, Campbell DJ. (2014). Regulatory T-cell homeostasis: steady-state maintenance and modulation during inflammation. Immunol Rev, 259(1), 40–59. doi: 10.1111/imr.12170.
   PubMed Web of Science ®Google Scholar
• Soares KC, Rucki AA, Kim V, et al. (2015). TGF-beta blockade depletes T regulatory cells from metastatic pancreatic tumors in a vaccine dependent manner. Oncotarget, 6(40), 43005–43015. doi: 10.18632/oncotarget.5656.
   PubMed Web of Science ®Google Scholar
• Sugihara S, Izumi Y, Yoshioka T, et al. (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.
   Google Scholar
• Sugiyama D, Nishikawa H, Maeda Y, et al. (2013). Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. Proc Natl Acad Sci USA, 110(44), 17945–17950. doi: 10.1073/pnas.1316796110.
   PubMed Web of Science ®Google Scholar
• Suzuki K, Kadota K, Sima CS, et al. (2013). Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor beta2 (IL-12Rbeta2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence. J Clin Oncol, 31(4), 490–498. doi: 10.1200/JCO.2012.45.2052.
   PubMed Web of Science ®Google Scholar
• Tada T, Taniguchi M, Takemori T. (1975). Properties of primed suppressor T cells and their products. Transplant Rev, 26, 106–29.
   PubMed Web of Science ®Google Scholar
• Tan MC, Goedegebuure PS, Belt BA, et al. (2009). Disruption of CCR5-dependent homing of regulatory T cells inhibits tumor growth in a murine model of pancreatic cancer. J Immunol, 182(3), 1746–1755.
   PubMed Web of Science ®Google Scholar
• Thornton AM, Korty PE, Tran DQ, et al. (2010). Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J Immunol, 184(7), 3433–3441. doi: 10.4049/jimmunol.0904028.
   PubMed Web of Science ®Google Scholar
• Valzasina B, Piconese S, Guiducci C, Colombo MP. (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. doi: 10.1158/0008-5472.CAN-05-4217.
   PubMed Web of Science ®Google Scholar
• Wainwright DA, Sengupta S, Han Y, Lesniak MS. (2011). Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors. Neuro Oncol, 13(12), 1308–1323. doi: 10.1093/neuonc/nor134.
   PubMed Web of Science ®Google Scholar
• Wald O, Izhar U, Amir G, et al. (2006). CD4+CXCR4highCD69+ T cells accumulate in lung adenocarcinoma. J Immunol, 177(10), 6983–6990.
   PubMed Web of Science ®Google Scholar
• Walter S, Weinschenk T, Stenzl A, et al. (2012). Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med, 18(8), 1254–1261. doi: 10.1038/nm.2883.
   PubMed Web of Science ®Google Scholar
• Wang C, Lee JH, Kim CH. (2012). Optimal population of FoxP3+ T cells in tumors requires an antigen priming-dependent trafficking receptor switch. PLoS One, 7(1), e30793. doi: 10.1371/journal.pone.0030793.
   PubMed Web of Science ®Google Scholar
• Wang HY, Lee DA, Peng G, et al. (2004). Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity, 20(1), 107–18.
   PubMed Web of Science ®Google Scholar
• Wang HY, Peng G, Guo Z, et al. (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.
   PubMed Web of Science ®Google Scholar
• Watanabe MA, Oda JM, Amarante MK, Cesar Voltarelli J. (2010). Regulatory T cells and breast cancer: implications for immunopathogenesis. Cancer Metastasis Rev, 29(4), 569–579. doi: 10.1007/s10555-010-9247-y.
   PubMed Web of Science ®Google Scholar
• Weiner HL, da Cunha AP, Quintana F, Wu H. (2011). Oral tolerance. Immunol Rev, 241(1), 241–259. doi: 10.1111/j.1600-065X.2011.01017.x.
   PubMed Web of Science ®Google Scholar
• Weiss JM, Bilate AM, Gobert M, et al. (2012). Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells. J Exp Med, 209(10), 1723–1742, S1. doi: 10.1084/jem.20120914.
   PubMed Web of Science ®Google Scholar
• Whiteside TL. (2012). What are regulatory T cells (Treg) regulating in cancer and why? Semin Cancer Biol, 22(4), 327–334. doi: 10.1016/j.semcancer.2012.03.004.
   PubMed Web of Science ®Google Scholar
• Whiteside TL, Schuler P, Schilling B. (2012). Induced and natural regulatory T cells in human cancer. Expert Opin Biol Ther, 12(10), 1383–1397. doi: 10.1517/14712598.2012.707184.
   PubMed Web of Science ®Google Scholar
• Wicherek L, Jozwicki W, Windorbska W, et al. (2011). Analysis of Treg cell population alterations in the peripheral blood of patients treated surgically for ovarian cancer - a preliminary report. Am J Reprod Immunol, 66(5), 444–450. doi: 10.1111/j.1600-0897.2011.01024.x.
   PubMed Web of Science ®Google Scholar
• Wieczorek G, Asemissen A, Model F, 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(2), 599–608. doi: 10.1158/0008-5472.CAN-08-2361.
   PubMed Web of Science ®Google Scholar
• Wolf D, Sopper S, Pircher A, et al. (2015). Treg(s) in cancer: Friends or foe? J Cell Physiol, 230(11), 2598–2605. doi: 10.1002/jcp.25016.
   Google Scholar
• Yadav M, Louvet C, Davini D, et al. (2012). Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. J Exp Med, 209( 10), 1713–1722, S1–19. doi: 10.1084/jem.20120822.
   PubMed Web of Science ®Google Scholar
• Yadav M, Stephan S, Bluestone JA. (2013). Peripherally induced tregs - role in immune homeostasis and autoimmunity. Front Immunol, 4, 232. doi: 10.3389/fimmu.2013.00232.
   PubMed Web of Science ®Google Scholar
• Yan M, Jene N, Byrne D, et al. (2011). Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers. Breast Cancer Res, 13(2), R47. doi: 10.1186/bcr2869.
   PubMed Web of Science ®Google Scholar
• Yoshii M, Tanaka H, Ohira M, et al. (2012). Expression of Forkhead box P3 in tumour cells causes immunoregulatory function of signet ring cell carcinoma of the stomach. Br J Cancer, 106(10), 1668–1674. doi: 10.1038/bjc.2012.141.
   PubMed Web of Science ®Google Scholar
• Zheng Y, Josefowicz S, Chaudhry A, et al. (2010). Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature, 463(7282), 808–812. doi: 10.1038/nature08750.
   PubMed Web of Science ®Google Scholar
• Zhou G, Drake CG, Levitsky HI. (2006). Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood, 107(2), 628–636. doi: 10.1182/blood-2005-07-2737.
   PubMed Web of Science ®Google Scholar
• Zhou G, Levitsky HI. (2007). Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance. J Immunol, 178(4), 2155–2162.
   Google Scholar
• Zhuo C, Li Z, Xu Y, et al. (2014). Higher FOXP3-TSDR demethylation rates in adjacent normal tissues in patients with colon cancer were associated with worse survival. Mol Cancer, 13, 153. doi: 10.1186/1476-4598-13-153.
   Google Scholar
• Zhuo C, Xu Y, Ying M, et al. (2015). FOXP3+ Tregs: heterogeneous phenotypes and conflicting impacts on survival outcomes in patients with colorectal cancer. Immunol Res, 61(3), 338–347. doi: 10.1007/s12026-014-8616-y.
   PubMed Web of Science ®Google Scholar
• Ziegler SF. (2006). FOXP3: of mice and men. Annu Rev Immunol, 24, 209–226. doi: 10.1146/annurev.immunol.24.021605.090547.
   PubMed Web of Science ®Google Scholar