[ 1 ] Prise KM, O’Sullivan JM. Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer 2009;9(5):351–60. link1

[ 2 ] Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363(8):711–23. link1

[ 3 ] Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366(26):2443–54. link1

[ 4 ] Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014;32(10):1020–30. link1

[ 5 ] Rizvi NA, Mazières J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol 2015;16 (3):257–65. link1

[ 6 ] Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 2015;373(17):1627–39. link1

[ 7 ] Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010;28(19):3167–75. link1

[ 8 ] Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, et al. Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther 2017;25(1):285–95. link1

[ 9 ] Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 2015;27(4):450–61. link1

[10] Shimizu J, Yamazaki S, Sakaguchi S. Induction of tumor immunity by removing CD25+ CD4+ T cells: a common basis between tumor immunity and autoimmunity. J Immunol 1999;163(10):5211–8. link1

[11] Jordan MS, Boesteanu A, Reed AJ, Petrone AL, Holenbeck AE, Lerman MA, et al. Thymic selection of CD4+ CD25+ regulatory T cells induced by an agonist selfpeptide. Nat Immunol 2001;2(4):301–6. link1

[12] Arce Vargas F, Furness AJS, Solomon I, Joshi K, Mekkaoui L, Lesko MH, et al. Fcoptimized anti-CD25 depletes tumor-infiltrating regulatory T cells and synergizes with PD-1 blockade to eradicate established tumors. Immunity 2017;46(4):577–86. link1

[13] Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 2007;317(5835):256–60. link1

[14] Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, et al. Conversion of peripheral CD4+ CD25- naive T cells to CD4+ CD25+ regulatory T cells by TGF-b induction of transcription factor Foxp3. J Exp Med 2003;198(12):1875–86. link1

[15] Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, et al. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 2002;297(5588):1867–70. link1

[16] Kim YC, Bhairavabhotla R, Yoon J, Golding A, Thornton AM, Tran DQ, et al. Oligodeoxynucleotides stabilize Helios-expressing Foxp3+ human T regulatory cells during in vitro expansion. Blood 2012;119(12):2810–8. link1

[17] Yadav M, Louvet C, Davini D, Gardner JM, Martinez-Llordella M, BaileyBucktrout S, et al. Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo. J Exp Med 2012;209 (10):1713–22. link1

[18] Okamura T, Fujio K, Sumitomo S, Yamamoto K. Roles of LAG3 and EGR2 in regulatory T cells. Ann Rheum Dis 2012;71(Suppl. 2):i96–100. link1

[19] Kim JK, Klinger M, Benjamin J, Xiao Y, Erle DJ, Littman DR, et al. Impact of the TCR signal on regulatory T cell homeostasis, function, and trafficking. PLoS One 2009;4(8):e6580. link1

[20] Kronenberg M, Rudensky A. Regulation of immunity by self-reactive T cells. Nature 2005;435(7042):598–604. link1

[21] Salomon B, Lenschow DJ, Rhee L, Ashourian N, Singh B, Sharpe A, et al. B7/ CD28 costimulation is essential for the homeostasis of the CD4+ CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 2000;12(4):431–40. link1

[22] Tai X, Cowan M, Feigenbaum L, Singer A. CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2. Nat Immunol 2005;6(2):152–62. link1

[23] D’Cruz LM, Klein L. Development and function of agonist-induced CD25+ Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol 2005;6(11):1152–9. link1

[24] Ruan Q, Kameswaran V, Tone Y, Li L, Liou HC, Greene MI, et al. Development of Foxp3+ regulatory T cells is driven by the c-Rel enhanceosome. Immunity 2009;31(6):932–40. link1

[25] Akiyama T, Maeda S, Yamane S, Ogino K, Kasai M, Kajiura F, et al. Dependence of self-tolerance on TRAF6-directed development of thymic stroma. Science 2005;308(5719):248–51. link1

[26] Overacre-Delgoffe AE, Chikina M, Dadey RE, Yano H, Brunazzi EA, Shayan G, et al. Interferon-c drives Treg fragility to promote anti-tumor immunity. Cell 2017;169(6):1130–41.e11. link1

[27] Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat Immunol 2003;4(4):330–6. link1

[28] Chen GY, Chen C, Wang L, Chang X, Zheng P, Liu Y. Cutting edge: broad expression of the FoxP3 locus in epithelial cells: a caution against early interpretation of fatal inflammatory diseases following in vivo depletion of FoxP3-expressing cells. J Immunol 2008;180(8):5163–6. link1

[29] Kalekar LA, Mueller DL. Relationship between CD4 regulatory T cells and anergy in vivo. J Immunol 2017;198(7):2527–33. link1

[30] Ohkura N, Hamaguchi M, Morikawa H, Sugimura K, Tanaka A, Ito Y, et al. T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. Immunity 2012;37(5):785–99. link1

[31] Povoleri GA, Scottà C, Nova-Lamperti EA, John S, Lombardi G, Afzali B. Thymic versus induced regulatory T cells—who regulates the regulators? Front Immunol 2013;4:169. link1

[32] Zheng Y, Josefowicz S, Chaudhry A, Peng XP, Forbush K, Rudensky AY. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 2010;463(7282):808–12. link1

[33] Yao Z, Kanno Y, Kerenyi M, Stephens G, Durant L, Watford WT, et al. Nonredundant roles for Stat5a/b in directly regulating Foxp3. Blood 2007;109 (10):4368–75. link1

[34] Nagar M, Vernitsky H, Cohen Y, Dominissini D, Berkun Y, Rechavi G, et al. Epigenetic inheritance of DNA methylation limits activation-induced expression of FOXP3 in conventional human CD25- CD4+ T cells. Int Immunol 2008;20(8):1041–55. link1

[35] Ouyang W, Beckett O, Ma Q, Paik JH, DePinho RA, Li MO. Foxo proteins cooperatively control the differentiation of Foxp3+ regulatory T cells. Nat Immunol 2010;11(7):618–27. link1

[36] Chen Z, Barbi J, Bu S, Yang HY, Li Z, Gao Y, et al. The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3. Immunity 2013;39(2):272–85. link1

[37] van Loosdregt J, Fleskens V, Fu J, et al. Stabilization of the transcription factor Foxp3 by the deubiquitinase USP7 increases Treg-cell-suppressive capacity. Immunity 2013;39(2):259–71. link1

[38] Li Y, Lu Y, Wang S, Han Z, Zhu F, Ni Y, et al. USP21 prevents the generation of T-helper-1-like Treg cells. Nat Commun 2016;7:13559. link1

[39] Li B, Samanta A, Song X, Iacono KT, Bembas K, Tao R, et al. FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repression. Proc Natl Acad Sci USA 2007;104(11):4571–6. link1

[40] Liu Y, Wang L, Predina J, Han R, Beier UH, Wang LC, et al. Inhibition of p300 impairs Foxp3+ T regulatory cell function and promotes antitumor immunity. Nat Med 2013;19(9):1173–7. link1

[41] van Loosdregt J, Brunen D, Fleskens V, Pals CE, Lam EW, Coffer PJ. Rapid temporal control of Foxp3 protein degradation by sirtuin-1. PLoS One 2011;6 (4):e19047. link1

[42] Kim HP, Leonard WJ. CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation. J Exp Med 2007;204 (7):1543–51. link1

[43] Read S, Malmström V, Powrie F. 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 2000;192(2):295–302. link1

[44] Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007;450(7169):566–9. link1

[45] Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med 1999;190(7):995–1004. link1

[46] Takahashi T, Kuniyasu Y, Toda M, Sakaguchi N, Itoh M, Iwata M, et al. 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 1998;10(12):1969–80. link1

[47] Wang Y, Mao Y, Zhang J, Shi G, Cheng L, Lin Y, et al. IL-35 recombinant protein reverses inflammatory bowel disease and psoriasis through regulation of inflammatory cytokines and immune cells. J Cell Mol Med 2018;22 (2):1014–25. link1

[48] Turnis ME, Sawant DV, Szymczak-Workman AL, Andrews LP, Delgoffe GM, Yano H, et al. Interleukin-35 limits anti-tumor immunity. Immunity 2016;44 (2):316–29. link1

[49] Kurschus FC, Kleinschmidt M, Fellows E, et al. Killing of target cells by redirected granzyme B in the absence of perforin. FEBS Lett 2004;562(1– 3):87–92. link1

[50] Gondek DC, Lu LF, Quezada SA, Sakaguchi S, Noelle RJ. Cutting edge: contactmediated suppression by CD4+ CD25+ regulatory cells involves a granzyme Bdependent, perforin-independent mechanism. J Immunol 2005;174 (4):1783–6. link1

[51] Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in Tcell clones. Nature 1992;356(6370):607–9. link1

[52] Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995;182(2):459–65. link1

[53] Magistrelli G, Jeannin P, Herbault N, Benoit De Coignac A, Gauchat JF, Bonnefoy JY, et al. A soluble form of CTLA-4 generated by alternative splicing is expressed by nonstimulated human T cells. Eur J Immunol 1999;29 (11):3596–602. link1

[54] Stephens GL, McHugh RS, Whitters MJ, Young DA, Luxenberg D, Carreno BM, et al. Engagement of glucocorticoid-induced TNFR family-related receptor on effector T cells by its ligand mediates resistance to suppression by CD4+ CD25+ T cells. J Immunol 2004;173(8):5008–20. link1

[55] Garín MI, Chu CC, Golshayan D, Cernuda-Morollón E, Wait R, Lechler RI. Galectin-1: a key effector of regulation mediated by CD4+ CD25+ T cells. Blood 2007;109(5):2058–65. link1

[56] Borsellino G, Kleinewietfeld M, Di Mitri D, Sternjak A, Diamantini A, Giometto R, et al. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 2007;110(4):1225–32. link1

[57] Kobie JJ, Shah PR, Yang L, Rebhahn JA, Fowell DJ, Mosmann TR. T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 50 -adenosine monophosphate to adenosine. J Immunol 2006;177(10):6780–6. link1

[58] Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ. CD4+ CD25+ Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol 2007;8(12):1353–62. link1

[59] Liang B, Workman C, Lee J, Chew C, Dale BM, Colonna L, et al. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II. J Immunol 2008;180(9):5916–26. link1

[60] Yu X, Harden K, Gonzalez LC, Francesco M, Chiang E, Irving B, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol 2009;10(1):48–57. link1

[61] Sarris M, Andersen KG, Randow F, Mayr L, Betz AG. Neuropilin-1 expression on regulatory T cells enhances their interactions with dendritic cells during antigen recognition. Immunity 2008;28(3):402–13. link1

[62] Fallarino F, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, et al. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 2003;4(12):1206–12. link1

[63] Maj T, Wang W, Crespo J, Zhang H, Wang W, Wei S, et al. Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1- blockade resistance in tumor. Nat Immunol 2017;18(12):1332–41. link1

[64] Powrie F, Leach MW, Mauze S, Caddle LB, Coffman RL. Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice. Int Immunol 1993;5(11):1461–71. link1

[65] Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, Whitesell L, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 2001;27 (1):20–1. link1

[66] Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB, Yasayko SA, et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 2001;27 (1):68–73. link1

[67] Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 2006;6:295–307. link1

[68] Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, Niwa A, et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 2009;30(6):899–911. link1

[69] Saito T, Nishikawa H, Wada H, Nagano Y, Sugiyama D, Atarashi K, et al. Two FOXP3+ CD4+ T cell subpopulations distinctly control the prognosis of colorectal cancers. Nat Med 2016;22(6):679–84. link1

[70] Crusz SM, Balkwill FR. Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol 2015;12(10):584–96. link1

[71] Erdman SE, Poutahidis T. Cancer inflammation and regulatory T cells. Int J Cancer 2010;127(4):768–79. link1

[72] Cipolletta D, Feuerer M, Li A, Kamei N, Lee J, Shoelson SE, et al. PPAR-c is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 2012;486(7404):549–53. link1

[73] Kolodin D, van Panhuys N, Li C, Magnuson AM, Cipolletta D, Miller CM, et al. Antigen- and cytokine-driven accumulation of regulatory T cells in visceral adipose tissue of lean mice. Cell Metab 2015;21(4):543–57. link1

[74] Burzyn D, Kuswanto W, Kolodin D, Shadrach JL, Cerletti M, Jang Y, et al. A special population of regulatory T cells potentiates muscle repair. Cell 2013;155(6):1282–95. link1

[75] Arpaia N, Green JA, Moltedo B, Arvey A, Hemmers S, Yuan S, et al. A distinct function of regulatory T cells in tissue protection. Cell 2015;162(5):1078–89. link1

[76] Ali N, Zirak B, Rodriguez RS, Pauli ML, Truong HA, Lai K, et al. Regulatory T cells in skin facilitate epithelial stem cell differentiation. Cell 2017;169(6). 1119–29.e11. link1

[77] Warburg O. On respiratory impairment in cancer cells. Science 1956;124 (3215):269–70. link1

[78] Pearce EL, Pearce EJ. Metabolic pathways in immune cell activation and quiescence. Immunity 2013;38(4):633–43. link1

[79] Locasale JW. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev Cancer 2013;13(8):572–83. link1

[80] Chang CH, Qiu J, O’Sullivan D, Buck MD, Noguchi T, Curtis JD, et al. Metabolic competition in the tumor microenvironment is a driver of cancer progression. Cell 2015;162(6):1229–41. link1

[81] Gobert M, Treilleux I, Bendriss-Vermare N, Bachelot T, Goddard-Leon S, Arfi V, et al. 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 2009;69(5):2000–9. link1

[82] Wei S, Kryczek I, Edwards RP, Zou L, Szeliga W, Banerjee M, et al. Interleukin- 2 administration alters the CD4+ FOXP3+ T-cell pool and tumor trafficking in patients with ovarian carcinoma. Cancer Res 2007;67(15):7487–94. link1

[83] Plitas G, Konopacki C, Wu K, Bos PD, Morrow M, Putintseva EV, et al. Regulatory T cells exhibit distinct features in human breast cancer. Immunity 2016;45(5):1122–34. link1

[84] Villarreal DO, L’Huillier A, Armington S, Mottershead C, Filippova EV, Coder BD, et al. Targeting CCR8 induces protective antitumor immunity and enhances vaccine-induced responses in colon cancer. Cancer Res 2018;78 (18):5340–8. link1

[85] De Simone M, Arrigoni A, Rossetti G, Gruarin P, Ranzani V, Politano C, et al. Transcriptional landscape of human tissue lymphocytes unveils uniqueness of tumor-infiltrating T regulatory cells. Immunity 2016;45(5):1135–47. link1

[86] Zheng C, Zheng L, Yoo JK, Guo H, Zhang Y, Guo X, et al. Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell 2017;169(7):1342–56.e16. link1

[87] Liakou CI, Kamat A, Tang DN, Chen H, Sun J, Troncoso P, et al. 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 USA 2008;105 (39):14987–92. link1

[88] Hodi FS, Butler M, Oble DA, Seiden MV, Haluska FG, Kruse A, et al. Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci USA 2008;105(8):3005–10. link1

[89] Peggs KS, Quezada SA, Chambers CA, Korman AJ, Allison JP. Blockade of CTLA- 4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. J Exp Med 2009;206 (8):1717–25. link1

[90] Park HJ, Park JS, Jeong YH, Son J, Ban YH, Lee BH, et al. PD-1 upregulated on regulatory T cells during chronic virus infection enhances the suppression of CD8+ T cell immune response via the interaction with PD-L1 expressed on CD8+ T cells. J Immunol 2015;194(12):5801–11. link1

[91] Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S. Stimulation of CD25+ CD4+ regulatory T cells through GITR breaks immunological selftolerance. Nat Immunol 2002;3(2):135–42. link1

[92] Bulliard Y, Jolicoeur R, Windman M, Rue SM, Ettenberg S, Knee DA, et al. Activating Fcc receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. J Exp Med 2013;210 (9):1685–93. link1

[93] Curti BD, Kovacsovics-Bankowski M, Morris N, Walker E, Chisholm L, Floyd K, et al. OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res 2013;73(24):7189–98. link1

[94] Bulliard Y, Jolicoeur R, Zhang J, Dranoff G, Wilson NS, Brogdon JL. OX40 engagement depletes intratumoral Tregs via activating FccRs, leading to antitumor efficacy. Immunol Cell Biol 2014;92(6):475–80. link1

[95] Ko K, Yamazaki S, Nakamura K, Nishioka T, Hirota K, Yamaguchi T, et al. Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+ CD25+ CD4+ regulatory T cells. J Exp Med 2005;202(7):885–91. link1

[96] Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, et al. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med 2014;370(11):1008–18. link1

[97] Ali K, Soond DR, Pineiro R, Hagemann T, Pearce W, Lim EL, et al. Inactivation of PI(3)K p110d breaks regulatory T-cell-mediated immune tolerance to cancer. Nature 2014;510(7505):407–11. link1

[98] Levin AM, Bates DL, Ring AM, Krieg C, Lin JT, Su L, et al. Exploiting a natural conformational switch to engineer an interleukin-2 ‘superkine’. Nature 2012;484(7395):529–33. link1

[99] Klapper JA, Downey SG, Smith FO, Yang JC, Hughes MS, Kammula US, et al. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma: a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer 2008;113(2):293–301. link1

[100] Jacobs JF, Punt CJ, Lesterhuis WJ, Sutmuller RP, Brouwer HM, Scharenborg NM, et al. Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I/II study in metastatic melanoma patients. Clin Cancer Res 2010;16(20):5067–78. link1

[101] Rech AJ, Mick R, Martin S, Recio A, Aqui NA, Powell DJ Jr, et al. CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients. Sci Transl Med 2012;4(134):134ra62. link1

[102] Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor a) monoclonal antibody. Cancer Res 1999;59(13):3128–33. link1

[103] Ghiringhelli F, Larmonier N, Schmitt E, Parcellier A, Cathelin D, Garrido C, et al. CD4+ CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol 2004;34(2):336–44. link1

[104] Motoyoshi Y, Kaminoda K, Saitoh O, Hamasaki K, Nakao K, Ishii N, et al. Different mechanisms for anti-tumor effects of low- and high-dose cyclophosphamide. Oncol Rep 2006;16(1):141–6. link1

[105] Ge Y, Domschke C, Stoiber N, Schott S, Heil J, Rom J, et al. Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome. Cancer Immunol Immunother 2012;61(3):353–62. link1

[106] Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, et al. Anti-CCR4 mAb selectively depletes effector-type FoxP3+ CD4+ regulatory T cells, evoking antitumor immune responses in humans. Proc Natl Acad Sci USA 2013;110(44):17945–50. link1

[107] Yi G, Guo S, Liu W, Wang H, Liu R, Tsun A, et al. Identification and functional analysis of heterogeneous FOXP3+ Treg cell subpopulations in human pancreatic ductal adenocarcinoma. Sci Bull 2018;63(15):792–981. link1

[108] Takeuchi Y, Nishikawa H. Roles of regulatory T cells in cancer immunity. Int Immunol 2016;28(8):401–9. link1

[109] Maeda Y, Nishikawa H, Sugiyama D, Ha D, Hamaguchi M, Saito T, et al. Detection of self-reactive CD8+ T cells with an anergic phenotype in healthy individuals. Science 2014;346(6216):1536–40. link1