T-Regulatory Cells In Tumor Progression And Therapy

References

• Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6 ):394–424. doi:10.3322/caac.v68.630207593
   PubMed Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674. doi:10.1016/j.cell.2011.02.01321376230
   PubMed Web of Science ®Google Scholar
• Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–1570. doi:10.1126/science.120348621436444
   PubMed Web of Science ®Google Scholar
• Cavallo F, De Giovanni C, Nanni P, et al. 2011: the immune hallmarks of cancer. Cancer Immunol Immunother. 2011;60:319–326. doi:10.1007/s00262-010-0968-021267721
   PubMed Web of Science ®Google Scholar
• Mougiakakos D, Choudhury A, Lladser A, et al. Regulatory T cells in cancer. Adv Cancer Res. 2010;107:57–117.20399961
   PubMed Web of Science ®Google Scholar
• Dwarakanath BS, Farooque A, Gupta S. Targeting regulatory T cells for improving cancer therapy: challenges and prospects. Cancer Rep. 2018;1:e21105. doi:10.1002/cnr2.1105
   Google Scholar
• Halvorsen EC, Mahmoud SM, Bennewith KL. Emerging roles of regulatory T cells in tumor progression and metastasis. Cancer Metastasis Rev. 2014;33(4 ):1025–1041. doi:10.1007/s10555-014-9529-x25359584
   PubMed Web of Science ®Google Scholar
• Akdis M, Blaser K, Akdis CA. T regulatory cells in allergy: novel concepts in the pathogenesis, prevention, and treatment of allergic diseases. J Allergy Clin Immunol. 2005;116:961–968. doi:10.1016/j.jaci.2005.09.00416275361
   PubMed Web of Science ®Google Scholar
• Demengeot J, Zelenay S, Moraes-Fontes MF, et al. Regulatory T cells in microbial infection. Springer Semin Immunopathol. 2006;28:41–50. doi:10.1007/s00281-006-0024-516874537
   PubMed Web of Science ®Google Scholar
• Shevach EM. Foxp3+ T regulatory cells: still many unanswered questions-A perspective after 20 years of study. Front Immunol. 2018;9:1048. doi:10.3389/fimmu.2018.0104829868011
   PubMed Web of Science ®Google Scholar
• Antony PA, Piccirillo CA, Akpinarli A, et al. 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. 2005;174:2591–2601. doi:10.4049/jimmunol.174.5.259115728465
   PubMed Web of Science ®Google Scholar
• Grauer OM, Nierkens S, Bennink E, et al. CD4+FoxP3+ regulatory T cells gradually accumulate in gliomas during tumor growth and efficiently suppress anti-glioma immune responses in vivo. Int J Cancer. 2007;121:95–105. doi:10.1002/(ISSN)1097-021517315190
   PubMed Web of Science ®Google Scholar
• Laronne-Bar-On A, Zipori D, Haran-Ghera N. Increased regulatory versus effector T cell development is associated with thymus atrophy in mouse models of multiple myeloma. J Immunol. 2008;181:3714–3724. doi:10.4049/jimmunol.181.5.371418714048
   PubMed Web of Science ®Google Scholar
• Liyanage UK, Moore TT, Joo HG, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002;169:2756–2761. doi:10.4049/jimmunol.169.5.275612193750
   PubMed Web of Science ®Google Scholar
• Marshall NA, Christie LE, Munro LR, et al. Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood. 2004;103:1755–1762. doi:10.1182/blood-2003-07-259414604957
   PubMed Web of Science ®Google Scholar
• Ormandy LA, Hillemann T, Wedemeyer H, et al. Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res. 2005;65:2457–2464. doi:10.1158/0008-5472.CAN-04-323215781662
   PubMed Web of Science ®Google Scholar
• Sasada T, Kimura M, Yoshida Y, et al. CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer. 2003;98:1089–1099. doi:10.1002/(ISSN)1097-014212942579
   PubMed Web of Science ®Google Scholar
• Schaefer C, Kim GG, Albers A, et al. Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer. Br J Cancer. 2005;92:913–920. doi:10.1038/sj.bjc.660240715714205
   PubMed Web of Science ®Google Scholar
• Shitara K, Nishikawa H. Regulatory T cells: a potential target in cancer immunotherapy. Ann N Y Acad Sci. 2018;1417(1 ):104–115. doi:10.1111/nyas.2018.1417.issue-129566262
   PubMed Web of Science ®Google Scholar
• Luther C, Swami U, Zhang J, et al. Advanced stage melanoma therapies: detailing the present and exploring the future. Crit Rev Oncol Hematol. 2019;133:99–111. doi:10.1016/j.critrevonc.2018.11.00230661664
   PubMed Web of Science ®Google Scholar
• Zhao H, Liao X, Kang Y. Tregs: where we are and what comes next? Front Immunol. 2017;8. doi:10.3389/fimmu.2017.01578
   Web of Science ®Google Scholar
• Han S, Toker A, Liu ZQ, Ohashi PS. Turning the tide against regulatory T cells. Front Oncol. 2019;9:279 eCollection 2019. doi:10.3389/fonc.2019.0027931058083
   PubMed Web of Science ®Google Scholar
• Schmidt A, Oberle N, Krammer PH. Molecular mechanisms of treg-mediated T cell suppression. Front Immunol. 2012;3:51 eCollection 2012. doi:10.3389/fimmu.2012.0005122566933
   PubMed Web of Science ®Google Scholar
• Lin YC, Chang LY, Huang CT, et al. Effector/memory but not naive regulatory T cells are responsible for the loss of concomitant tumor immunity. J Immunol. 2009;182:6095–6104. doi:10.4049/jimmunol.080382919414761
   PubMed Web of Science ®Google Scholar
• Turk MJ, Guevara-Patino JA, Rizzuto GA, et al. Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells. J Exp Med. 2004;200:771–782. doi:10.1084/jem.2004113015381730
   PubMed Web of Science ®Google Scholar
• Bates GJ, Fox SB, Han C, et al. Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 2006;24:5373–5380. doi:10.1200/JCO.2006.05.958417135638
   PubMed Web of Science ®Google Scholar
• Okita R, Saeki T, Takashima S, et al. CD4+CD25+ regulatory T cells in the peripheral blood of patients with breast cancer and non-small cell lung cancer. Oncol Rep. 2005;14:1269–1273.16211295
   PubMed Web of Science ®Google Scholar
• Bergmann C, Strauss L, Wang Y, et al. T regulatory type 1 cells in squamous cell carcinoma of the head and neck: mechanisms of suppression and expansion in advanced disease. Clin Cancer Res. 2008;14:3706–3715. doi:10.1158/1078-0432.CCR-07-512618559587
   PubMed Web of Science ®Google Scholar
• Hiraoka N, Onozato K, Kosuge T, et al. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res. 2006;12:5423–5434. doi:10.1158/1078-0432.CCR-06-036917000676
   PubMed Web of Science ®Google Scholar
• Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10:942–949. doi:10.1038/nm109315322536
   PubMed Web of Science ®Google Scholar
• Tanaka H, Tanaka J, Kjaergaard J, et al. Depletion of CD4+ CD25+ regulatory cells augments the generation of specific immune T cells in tumor-draining lymph nodes. J Immunother. 2002;25:207–217. doi:10.1097/00002371-200205000-0000312000862
   PubMed Web of Science ®Google Scholar
• Prasad SJ, Farrand KJ, Matthews SA, et al. Dendritic cells loaded with stressed tumor cells elicit long-lasting protective tumor immunity in mice depleted of CD4+CD25+ regulatory T cells. J Immunol. 2005;174:90–98. doi:10.4049/jimmunol.174.1.9015611231
   PubMed Web of Science ®Google Scholar
• Wing K, Onishi Y, Prieto-Martin P, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 2008;322:271–275. doi:10.1126/science.116006218845758
   PubMed Web of Science ®Google Scholar
• Callahan MK, Wolchok JD, Allison JP. Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy. Semin Oncol. 2010;37:473–484. doi:10.1053/j.seminoncol.2010.09.00121074063
   PubMed Web of Science ®Google Scholar
• Knutson KL, Disis ML, Salazar LG. CD4 regulatory T cells in human cancer pathogenesis. Cancer Immunol Immunother. 2007;56:271–285. doi:10.1007/s00262-006-0194-y16819631
   PubMed Web of Science ®Google Scholar
• McHugh RS, Whitters MJ, Piccirillo CA, et al. CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity. 2002;16:311–323. doi:10.1016/S1074-7613(02)00280-711869690
   PubMed Web of Science ®Google Scholar
• Ko K, Yamazaki S, Nakamura K, 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;202:885–891. doi:10.1084/jem.2005094016186187
   PubMed Web of Science ®Google Scholar
• Hirschhorn-Cymerman D, Rizzuto GA, Merghoub T, et al. OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis. J Exp Med. 2009;206:1103–1116. doi:10.1084/jem.2008220519414558
   PubMed Web of Science ®Google Scholar
• Hegde U, Chhabra A, Chattopadhyay S, et al. Presence of low dose of fludarabine in cultures blocks regulatory T cell expansion and maintains tumor-specific cytotoxic T lymphocyte activity generated with peripheral blood lymphocytes. Pathobiology. 2008;75:200–208. doi:10.1159/00012498118550918
   PubMed Web of Science ®Google Scholar
• Correale P, Cusi MG, Tsang KY, et al. Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong immunologic and antitumor activity in metastatic colon cancer patients. J Clin Oncol. 2005;23:8950–8958. doi:10.1200/JCO.2005.12.14716061910
   PubMed Web of Science ®Google Scholar
• Barni S, Lissoni P, Paolorossi F, et al. Mitoxantrone as a single agent in pretreated metastatic breast cancer: effects on T lymphocyte subsets and their relation to clinical response. Tumori. 1991;77:227–231. doi:10.1177/0300891691077003081862550
   PubMed Web of Science ®Google Scholar
• Dwarakanath BS, Singh D, Banerji AK, et al. Clinical studies for improving radiotherapy with 2-deoxy-D-glucose: present status and future prospects. J Cancer Res Ther. 2009;5 Suppl 1:S21–S26. doi:10.4103/0973-1482.5513620009289
   PubMed Web of Science ®Google Scholar
• Farooque A, Singh N, Adhikari JS, et al. Enhanced antitumor immunity contributes to the radio-sensitization of ehrlich ascites tumor by the glycolytic inhibitor 2-deoxy-D-glucose in mice. PLoS One. 2014;9:e108131. doi:10.1371/journal.pone.010813125248151
   PubMed Web of Science ®Google Scholar
• Szylberg L, Karbownik D, Marszalek A. Role of FOXP3 in human cancers. Anticancer Res. 2016;36(8 ):3789–3794.27466478
   PubMed Web of Science ®Google Scholar
• Lee W, Lee GR. Transcriptional regulation and development of regulatory T cells. Exp Mol Med. 2018;50:e456. doi:10.1038/emm.2017.31329520112
   PubMed Web of Science ®Google Scholar
• Kitagawa Y, Ohkura N, Kidani Y, et al. Guidance of regulatory T cell development by Satb1-dependent super-enhancer establishment. Nat Immunol. 2016;18:173–183. doi:10.1038/ni.364627992401
   PubMed Web of Science ®Google Scholar
• Zhao D-M, Xue -H-H. MLL4 keeps Foxp3 in the loop. Nat Immunol. 2017;18:957–958. doi:10.1038/ni.381128829449
   PubMed Web of Science ®Google Scholar
• Tone Y, Furuuchi K, Kojima Y, et al. Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nat Immunol. 2008;9:194–202. doi:10.1038/ni154918157133
   PubMed Web of Science ®Google Scholar
• Zheng Y, Josefowicz S, Chaudhry A, et al. Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature. 2010;463:808–812. doi:10.1038/nature0875020072126
   PubMed Web of Science ®Google Scholar
• Kim H-P, Leonard WJ. CREB/ATF-dependent T cell receptor-induced FoxP3 gene expression: a role for DNA methylation. J Exp Med. 2007;204:1543–1551. doi:10.1084/jem.2007010917591856
   PubMed Web of Science ®Google Scholar
• Burchill MA, Yang J, Vogtenhuber C, et al. IL-2 receptor beta-dependent STAT5 activation is required for the development of Foxp3+ regulatory T cells. J Immunol. 2007;178:280–290. doi:10.4049/jimmunol.178.1.28017182565
   PubMed Web of Science ®Google Scholar
• Kitoh A, Ono M, Naoe Y, et al. Indispensable role of the Runx1-Cbfbeta transcription complex for in vivo-suppressive function of FoxP3+ regulatory T cells. Immunity. 2009;31:609–620. doi:10.1016/j.immuni.2009.09.00319800266
   PubMed Web of Science ®Google Scholar
• Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev. 2012;241:260–268. doi:10.1111/j.1600-065X.2011.01018.x
   Web of Science ®Google Scholar
• Galgani M, Rosa VD, Cava AL, Matarese G. Role of metabolism in the immunobiology of regulatory T cells. J Immunol. 2016;197(7 ):2567–2575. doi:10.4049/jimmunol.160024227638939
   PubMed Web of Science ®Google Scholar
• Jacobs SR, Herman CE, Maciver NJ, et al. Glucose uptake is limiting in T cell activation and requires CD28- mediated AKT-dependent and independent pathways. J Immunol. 2008;180:4476–4486. doi:10.4049/jimmunol.180.7.447618354169
   PubMed Web of Science ®Google Scholar
• Gupta S, Roy A, Dwarakanath BS. Metabolic cooperation and competition in the tumor microenvironment: implications for therapy. Front Oncol. 2017;7:68.28447025
   PubMed Web of Science ®Google Scholar
• Liu S, Sun X, Luo J, et al. Effects of radiation on T regulatory cells in normal states and cancer: mechanisms and clinical implications. Am J Cancer Res. 2015;5(11 ):3276–3285.26807310
   PubMed Web of Science ®Google Scholar
• Takeuchi Y, Nishikawa H. Roles of regulatory T cells in cancer immunity. Int Immunol. 2016;28:401–409. doi:10.1093/intimm/dxw02527160722
   PubMed Web of Science ®Google Scholar
• Ohue Y, Nishikawa H, Regulatory T. (Treg) cells in cancer: can Treg cells be a new therapeutic target? Cancer Sci. 2019;110(7 ):2080–2089. doi:10.1111/cas.1406931102428
   PubMed Web of Science ®Google Scholar
• Pandiyan P, Lenardo MJ. The control of CD4+CD25+Foxp3+ regulatory T cell survival. Biol Direct. 2008;3:6. doi:10.1186/1745-6150-3-618304352
   PubMed Web of Science ®Google Scholar
• Vincenti F, Kirkman R, Light S, et al. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. N Engl J Med. 1998;338:161–165. doi:10.1056/NEJM1998011533803049428817
   PubMed Web of Science ®Google Scholar
• 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;163:5211–5218.10553041
   PubMed Web of Science ®Google Scholar
• Onizuka S, Tawara I, Shimizu J, et al. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res. 1999;59:3128–3133.10397255
   PubMed Web of Science ®Google Scholar
• Jacobs JF, Punt CJ, Lesterhuis WJ, 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;16:5067–5078. doi:10.1158/1078-0432.CCR-10-175720736326
   PubMed Web of Science ®Google Scholar
• Mitchell DA, Cui X, Schmittling RJ, et al. Monoclonal antibody blockade of IL-2 receptor alpha during lymphopenia selectively depletes regulatory T cells in mice and humans. Blood. 2011;118:3003–3012. doi:10.1182/blood-2011-02-33456521768296
   PubMed Web of Science ®Google Scholar
• De Vries IJ, Castelli C, Huygens C, et al. Frequency of circulating Tregs with demethylated FOXP3 intron 1 in melanoma patients receiving tumor vaccines and potentially Treg-depleting agents. Clin Cancer Res. 2011;17:841–848. doi:10.1158/1078-0432.CCR-10-222721177412
   PubMed Web of Science ®Google Scholar
• Gabler C, Blank N, Hieronymus T, et al. Extranuclear detection of histones and nucleosomes in activated human lymphoblasts as an early event in apoptosis. Ann Rheum Dis. 2004;63:1135–1144. doi:10.1136/ard.2003.01145215308524
   PubMed Web of Science ®Google Scholar
• Hansel TT, Kropshofer H, Singer T, et al. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov. 2010;9:325–338. doi:10.1038/nrd300320305665
   PubMed Web of Science ®Google Scholar
• Martinelli V, Dalla Costa G, Sangalli F, et al. Severe disease activity in a patient with multiple sclerosis after daclizumab discontinuation. Mult Scler Relat Disord. 2019;28:57–59. doi:10.1016/j.msard.2018.11.03430554038
   PubMed Web of Science ®Google Scholar
• Powell DJ Jr., Attia P, Ghetie V, et al. Partial reduction of human FOXP3+ CD4 T cells in vivo after CD25-directed recombinant immunotoxin administration. J Immunother. 2008;31:189–198. doi:10.1097/CJI.0b013e31815dc0e818481388
   PubMed Web of Science ®Google Scholar
• Syn NL, Teng MWL, Mok TSK, et al. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol. 2017;18(12 ):e731–e741. doi:10.1016/S1470-2045(17)30607-129208439
   PubMed Web of Science ®Google Scholar
• Takahashi T, Tagami T, Yamazaki S, et al. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med. 2000;192:303–310. doi:10.1084/jem.192.2.30310899917
   PubMed Web of Science ®Google Scholar
• Read S, Malmstrom 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;192:295–302.10899916
   PubMed Web of Science ®Google Scholar
• Greenfield EA, Nguyen KA, Kuchroo VK. CD28/B7 costimulation: a review. Crit Rev Immunol. 1998;18:389–418. doi:10.1615/CritRevImmunol.v18.i59784967
   PubMed Web of Science ®Google Scholar
• Fallarino F, Grohmann U, You S, et al. 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. 2006;176:6752–6761. doi:10.4049/jimmunol.176.11.675216709834
   PubMed Web of Science ®Google Scholar
• Walker LS. Treg and CTLA-4: two intertwining pathways to immune tolerance. J Autoimmun. 2013;45:49–57. doi:10.1016/j.jaut.2013.06.00623849743
   PubMed Web of Science ®Google Scholar
• Kavanagh B, O’Brien S, Lee D, et al. CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion. Blood. 2008;112:1175–1183. doi:10.1182/blood-2007-11-12543518523152
   PubMed Web of Science ®Google Scholar
• Hurwitz AA, Foster BA, Kwon ED, et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res. 2000;60:2444–2448.10811122
   PubMed Web of Science ®Google Scholar
• Kwon ED, Foster BA, Hurwitz AA, et al. Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade immunotherapy. Proc Natl Acad Sci U S A. 1999;96:15074–15079. doi:10.1073/pnas.96.26.1507410611340
   PubMed Web of Science ®Google Scholar
• Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271:1734–1736. doi:10.1126/science.271.5256.17348596936
   PubMed Web of Science ®Google Scholar
• Hodi FS. Overcoming immunological tolerance to melanoma: targeting CTLA-4. Asia Pac J Clin Oncol. 2010;6 Suppl 1:S16–S23. doi:10.1111/j.1743-7563.2010.01271.x20482528
   PubMed Web of Science ®Google Scholar
• Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384(9948 ):1109–1117. doi:10.1016/S0140-6736(14)60958-225034862
   PubMed Web of Science ®Google Scholar
• Topalian SL, Drake CG, Pardoll DM. Targeting PD-1/B7-H1 (PD-L1) pathway to activate antitumor immunity. Curr Opin Immunol. 2012;24:207–212. doi:10.1016/j.coi.2011.12.00922236695
   PubMed Web of Science ®Google Scholar
• Kumar S, Malik S, Singh UP, et al. PD-1 expression on Foxp3+ Treg cells modulates CD8+ T cell function in prostate tumor microenvironment. J Immunol. 2017;198(1 Supplement ):155.11.
   Web of Science ®Google Scholar
• Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206:3015–3029. doi:10.1084/jem.2009084720008522
   PubMed Web of Science ®Google Scholar
• Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–2454. doi:10.1056/NEJMoa120069022658127
   PubMed Web of Science ®Google Scholar
• Woods DM, Ramakrishnan R, Sodré AL, et al. PD-1 blockade induces phosphorylated STAT3 and results in an increase of Tregs with reduced suppressive function. J Immunol. 2017;198:56.7.
   PubMed Web of Science ®Google Scholar
• Kamada T, Togashi Y, Tay C, et al. PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc Natl Acad Sci U S A. 2019;116(20 ):9999–10008. doi:10.1073/pnas.182200111631028147
   PubMed Web of Science ®Google Scholar
• Shevach EM, Stephens GL. The GITR-GITRL interaction: co-stimulation or contrasuppression of regulatory activity? Nat Rev Immunol. 2006;6:613–618. doi:10.1038/nri186716868552
   PubMed Web of Science ®Google Scholar
• Kanamaru F, Youngnak P, Hashiguchi M, et al. Costimulation via glucocorticoid-induced TNF receptor in both conventional and CD25+ regulatory CD4+ T cells. J Immunol. 2004;172:7306–7314. doi:10.4049/jimmunol.172.12.730615187106
   PubMed Web of Science ®Google Scholar
• Ephrem A, Epstein AL, Stephens GL, et al. Modulation of Treg cells/T effector function by GITR signaling is context-dependent. Eur J Immunol. 2013;43:2421–2429. doi:10.1002/eji.20134345123722868
   PubMed Web of Science ®Google Scholar
• Cohen AD, Diab A, Perales MA, et al. Agonist anti-GITR antibody enhances vaccine-induced CD8(+) T-cell responses and tumor immunity. Cancer Res. 2006;66:4904–4912. doi:10.1158/0008-5472.CAN-05-281316651447
   PubMed Web of Science ®Google Scholar
• Zappasodi R, Sirard C, Li Y, et al. Rational design of anti-GITR-based combination immunotherapy. Nat Med. 2019;25:759–766. doi:10.1038/s41591-019-0420-831036879
   PubMed Web of Science ®Google Scholar
• Pruitt SK, Boczkowski D, de Rosa N, et al. Enhancement of anti-tumor immunity through local modulation of CTLA-4 and GITR by dendritic cells. Eur J Immunol. 2011;41:3553–3563. doi:10.1002/eji.v41.1222028176
   PubMed Web of Science ®Google Scholar
• Nocentini G, Giunchi L, Ronchetti S, et al. A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis. Proc Natl Acad Sci U S A. 1997;94:6216–6221. doi:10.1073/pnas.94.12.62169177197
   PubMed Web of Science ®Google Scholar
• Kwon B, Yu KY, Ni J, et al. Identification of a novel activation-inducible protein of the tumor necrosis factor receptor superfamily and its ligand. J Biol Chem. 1999;274:6056–6061. doi:10.1074/jbc.274.10.605610037686
   PubMed Web of Science ®Google Scholar
• Croft M. Co-stimulatory members of the TNFR family: keys to effective T-cell immunity? Nat Rev Immunol. 2003;3:609–620. doi:10.1038/nri114812974476
   PubMed Web of Science ®Google Scholar
• Watts TH. TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol. 2005;23:23–68. doi:10.1146/annurev.immunol.23.021704.11583915771565
   PubMed Web of Science ®Google Scholar
• Piconese S, Valzasina B, Colombo MP. OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection. J Exp Med. 2008;205:825–839. doi:10.1084/jem.2007134118362171
   PubMed Web of Science ®Google Scholar
• Burocchi A, Pittoni P, Gorzanelli A, et al. Intratumor OX40 stimulation inhibits IRF1 expression and IL-10 production by Treg cells while enhancing CD40L expression by effector memory T cells. Eur J Immunol. 2011;41:3615–3626. doi:10.1002/eji.v41.1222229156
   PubMed Web of Science ®Google Scholar
• Pardee AD, McCurry D, Alber S, et al. A therapeutic OX40 agonist dynamically alters dendritic, endothelial, and T cell subsets within the established tumor microenvironment. Cancer Res. 2010;70:9041–9052. doi:10.1158/0008-5472.CAN-10-136921045144
   PubMed Web of Science ®Google Scholar
• Shrimali R, Ahmad S, Verma V, et al. concurrent PD-1 blockade negates the effects of OX40 agonist antibody in combination immunotherapy through inducing T-cell apoptosis. Cancer Immunol Res. 2017;5(9 ):755–766. doi:10.1158/2326-6066.CIR-17-029228848055
   PubMed Web of Science ®Google Scholar
• Walker LS. Regulatory T cells: folate receptor 4: a new handle on regulation and memory? Immunol Cell Biol. 2007;85:506–507. doi:10.1038/sj.icb.710011517710105
   PubMed Web of Science ®Google Scholar
• Yamaguchi T, Hirota K, Nagahama K, et al. Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity. 2007;27:145–159. doi:10.1016/j.immuni.2007.04.01717613255
   PubMed Web of Science ®Google Scholar
• Stover PJ. Physiology of folate and vitamin B12 in health and disease. Nutr Rev. 2004;62(6 Pt 2 ):S3–S12; discussion S13. doi:10.1111/j.1753-4887.2004.tb00070.x
   PubMed Web of Science ®Google Scholar
• Ghiringhelli F, Larmonier N, Schmitt E, 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;34:336–344. doi:10.1002/(ISSN)1521-414114768038
   PubMed Web of Science ®Google Scholar
• Proietti E, Greco G, Garrone B, et al. Importance of cyclophosphamide-induced bystander effect on T cells for a successful tumor eradication in response to adoptive immunotherapy in mice. J Clin Invest. 1998;101:429–441. doi:10.1172/JCI13489435316
   PubMed Web of Science ®Google Scholar
• Lynch JP, Derhovanessian A, Tazelaar H, et al. Granulomatosis with polyangiitis (Wegener’s Granulomatosis): evolving concepts in treatment. Semin Respir Crit Care Med. 2018;39(4 ):434–458. doi:10.1055/s-0038-166087430404111
   PubMed Web of Science ®Google Scholar
• Motoyoshi Y, Kaminoda K, Saitoh O, et al. Different mechanisms for anti-tumor effects of low- and high-dose cyclophosphamide. Oncol Rep. 2006;16(1 ):141–146.16786137
   PubMed Web of Science ®Google Scholar
• Berd D, Mastrangelo MJ. Effect of low dose cyclophosphamide on the immune system of cancer patients: depletion of CD4+, 2H4+ suppressor-inducer T-cells. Cancer Res. 1988;48:1671–1675.2830969
   PubMed Web of Science ®Google Scholar
• Awwad M, North RJ. Cyclophosphamide-induced immunologically mediated regression of a cyclophosphamide-resistant murine tumor: a consequence of eliminating precursor L3T4+ suppressor T-cells. Cancer Res. 1989;49:1649–1654.2522344
   PubMed Web of Science ®Google Scholar
• Awwad M, North RJ. Cyclophosphamide (Cy)-facilitated adoptive immunotherapy of a Cy-resistant tumour. Evidence that Cy permits the expression of adoptive T-cell mediated immunity by removing suppressor T cells rather than by reducing tumour burden. Immunology. 1988;65:87–92.2972604
   PubMed Web of Science ®Google Scholar
• Ercolini AM, Ladle BH, Manning EA, et al. Recruitment of latent pools of high-avidity CD8(+) T cells to the antitumor immune response. J Exp Med. 2005;201:1591–1602.15883172
   PubMed Web of Science ®Google Scholar
• Zhang H, Chua KS, Guimond M, et al. Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med. 2005;11:1238–1243. doi:10.1038/nm131216227988
   PubMed Web of Science ®Google Scholar
• Sharabi A, Haran-Ghera N. Immune recovery after cyclophosphamide treatment in multiple myeloma: implication for maintenance immunotherapy. Bone Marrow Res. 2011;2011:269519. doi:10.1155/2011/26951922046558
   PubMedGoogle Scholar
• Farooque A, Singh N, Verma A, et al. Immuno-modulation linked to the depletion of T regulatory cells contributes to the radio-sensitization of tumors by the glycolytic inhibitor 2-Deoxy-D-Glucose. J Cancer Res Therap. 2012;8:502.
   Google Scholar
• Farooque A, Verma A, Adhikari JS, et al. Targeting T-regulatory cells (CD4+CD25highFoxP3+) by the glycolytic inhibitor 2-Deoxy-D-Glucose (2-DG): implications in radiotherapy. J Adv Biotech. 2010;10:113.
   Google Scholar
• Audia S, Nicolas A, Cathelin D, et al. Increase of CD4+ CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma: a Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+ CD25+ T lymphocytes. Clin Exp Immunol. 2007;150:523–530. doi:10.1111/(ISSN)1365-224917956583
   PubMed Web of Science ®Google Scholar
• Nakahara T, Uchi H, Lesokhin AM, et al. Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs. Blood. 2010;115:4384–4392. doi:10.1182/blood-2009-11-25123120154220
   PubMed Web of Science ®Google Scholar
• Garcia AA, Hirte H, Fleming G, et al. Phase II clinical trial of bevacizumab and low-dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol. 2008;26:76–82. doi:10.1200/JCO.2007.12.193918165643
   PubMed Web of Science ®Google Scholar
• Greten TF, Ormandy LA, Fikuart A, et al. Low-dose cyclophosphamide treatment impairs regulatory T cells and unmasks AFP-specific CD4+ T-cell responses in patients with advanced HCC. J Immunother. 2010;33:211–218. doi:10.1097/CJI.0b013e3181bb499f20139774
   PubMed Web of Science ®Google Scholar
• Nizar S, Copier J, Meyer B, et al. T-regulatory cell modulation: the future of cancer immunotherapy? Br J Cancer. 2009;100:1697–1703. doi:10.1038/sj.bjc.660504019384299
   PubMed Web of Science ®Google Scholar
• Obeid M, Tesniere A, Ghiringhelli F, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13:54–61. doi:10.1038/nm152317187072
   PubMed Web of Science ®Google Scholar
• Polanczyk MJ, Hopke C, Vandenbark AA, et al. Estrogen-mediated immunomodulation involves reduced activation of effector T cells, potentiation of Treg cells, and enhanced expression of the PD-1 costimulatory pathway. J Neurosci Res. 2006;84:370–378. doi:10.1002/(ISSN)1097-454716676326
   PubMed Web of Science ®Google Scholar
• Prieto GA, Rosenstein Y. Oestradiol potentiates the suppressive function of human CD4 CD25 regulatory T cells by promoting their proliferation. Immunology. 2006;118:58–65. doi:10.1111/j.1365-2567.2006.02339.x16630023
   PubMed Web of Science ®Google Scholar
• Jiao J, Xiang H, Liao Q. Recent advancement in nonsteroidal aromatase inhibitors for treatment of estrogen-dependent breast cancer. Curr Med Chem. 2010;17:3476–3487. doi:10.2174/09298671079292787720738251
   PubMed Web of Science ®Google Scholar
• Generali D, Bates G, Berruti A, et al. Immunomodulation of FOXP3+ regulatory T cells by the aromatase inhibitor letrozole in breast cancer patients. Clin Cancer Res. 2009;15:1046–1051. doi:10.1158/1078-0432.CCR-08-150719188178
   PubMed Web of Science ®Google Scholar
• Phillips KA, Ribi K, Fisher R. Do aromatase inhibitors have adverse effects on cognitive function? Breast Cancer Res. 2011;13:203. doi:10.1186/bcr280621392408
   PubMed Web of Science ®Google Scholar
• Warburg O. The Metabolism of Tumors. London: Constable and Co.; 1930.
   Google Scholar
• Adhikari JS, Dwarakanath BS, Mathur R, Ravindranath T. Alterations in radiation induced cell cycle perturbations by 2-deoxy-D-glucose in human tumor cell lines. Indian J Exp Biol. 2003;41:1392–1399.15320491
   PubMedGoogle Scholar
• Dwarakanath B, Jain V. Targeting glucose metabolism with 2-deoxy-D-glucose for improving cancer therapy. Future Oncol. 2009;5:581–585. doi:10.2217/fon.09.4419519197
   PubMed Web of Science ®Google Scholar
• Dwarakanath BS. Cytotoxicity, radiosensitization, and chemosensitization of tumor cells by 2-deoxy-D-glucose in vitro. J Cancer Res Ther. 2009;5 Suppl 1:S27–S31. doi:10.4103/0973-1482.5513720009290
   PubMed Web of Science ®Google Scholar
• Dwarakanath BS, Singh S, Jain V. Optimization of tumour radiotherapy: part V Radiosensitization by 2-deoxy-D-glucose and DNA ligand Hoechst-33342 in a murine tumour. Indian J Exp Biol. 1999;37:865–870.10687280
   PubMedGoogle Scholar
• Gupta S, Farooque A, Adhikari JS, Singh S, Dwarakanath BS. Enhancement of radiation and chemotherapeutic drug responses by 2-deoxy-D-glucose in animal tumors. J Cancer Res Ther. 2009;5 Suppl 1:S16–S20. doi:10.4103/0973-1482.5513520009287
   PubMed Web of Science ®Google Scholar
• Mohanti BK, Rath GK, Anantha N, et al. Improving cancer radiotherapy with 2-deoxy-D-glucose: phase I/II clinical trials on human cerebral gliomas. Int J Radiat Oncol Biol Phys. 1996;35:103–111. doi:10.1016/S0360-3016(96)85017-68641905
   PubMed Web of Science ®Google Scholar
• Singh D, Banerji AK, Dwarakanath BS, et al. Optimizing cancer radiotherapy with 2-deoxy-d-glucose dose escalation studies in patients with glioblastoma multiforme. Strahlenther Onkol. 2005;181:507–514. doi:10.1007/s00066-005-1320-z16044218
   PubMed Web of Science ®Google Scholar
• Venkataramanaa NK, Venkatesh PK, Dwarakanath BS, Vani S. Protective effect on normal brain tissue during a combinational therapy of 2-deoxy-d-glucose and hypofractionated irradiation in malignant gliomas. Asian J Neurosurg. 2013;8:9–14. doi:10.4103/1793-5482.11027423741257
   PubMedGoogle Scholar
• Gupta S, Mathur R, Dwarakanath BS. The glycolytic inhibitor 2-deoxy-D-glucose enhances the efficacy of etoposide in ehrlich ascites tumor-bearing mice. Cancer Biol Ther. 2005;4:87–94. doi:10.4161/cbt.4.1.138115711125
   PubMed Web of Science ®Google Scholar
• De Rosa V, Galgani M, Porcellini A, et al. Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants. Nat Immunol. 2015;16:1174–1184. doi:10.1038/ni.326926414764
   PubMed Web of Science ®Google Scholar
• Farooque A, Afrin F, Adhikari JS, Dwarakanath BS. Protection of normal cells and tissues during radio- and chemosensitization of tumors by 2-deoxy-D-glucose. J Cancer Res Ther. 2009;5 Suppl 1:S32–S35. doi:10.4103/0973-1482.5513820009291
   PubMed Web of Science ®Google Scholar
• Almeida L, Lochner M, Berod L, et al. Metabolic pathways in T cell activation and lineage differentiation. Semin Immunol. 2016;28(5 ):514–524. doi:10.1016/j.smim.2016.10.00927825556
   PubMed Web of Science ®Google Scholar
• Persa E, Balogh A, Safrany G, et al. The effect of ionizing radiation on regulatory T cells in health and disease. Cancer Lett. 2015;368(2 ):252–261. doi:10.1016/j.canlet.2015.03.00325754816
   PubMed Web of Science ®Google Scholar
• Kachikwu EL, Iwamoto KS, Liao YP, et al. Radiation enhances regulatory T cell representation. Int J Radiat Oncol Biol Phys. 2011;81(4 ):1128–1135. doi:10.1016/j.ijrobp.2010.09.03421093169
   PubMed Web of Science ®Google Scholar
• Kershaw MH, Devaud C, John LB, Westwood JA, Darcy PK. Enhancing immunotherapy using chemotherapy and radiation to modify the tumor microenvironment. Oncoimmunology. 2013;2:e25962. doi:10.4161/onci.2596224327938
   PubMed Web of Science ®Google Scholar
• Patel MA, Kim JE, Theodros D, et al. Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immunemediated survival advantage in murine intracranial glioma. J Immuno Ther Cancer. 2016;4:28. doi:10.1186/s40425-016-0132-2
   PubMed Web of Science ®Google Scholar
• Cao M, Cabrera R, Xu Y, et al. Gamma irradiation alters the phenotype and function of CD4+CD25+ regulatory T cells. Cell Biol Int. 2009;33:565–571. doi:10.1016/j.cellbi.2009.02.00719268553
   PubMed Web of Science ®Google Scholar
• Muroyama Y, Nirschl TR, Kochel CM, et al. Stereotactic radiotherapy increases functionally suppressive regulatory T cells in the tumor microenvironment. Cancer Immunol Res. 2017;5(11 ):992–1004. doi:10.1158/2326-6066.CIR-17-004028970196
   PubMed Web of Science ®Google Scholar
• Oweida AJ, Darragh L, Phan A, et al. STAT3 modulation of regulatory T cells in response to radiation therapy in head and neck cancer. J Natl Cancer Inst. 2019; djz036 [Epub ahead of print]. doi:10.1093/jnci/djz036.
   Google Scholar
• Mignot G, Roux S, Thery C, Segura E, Zitvogel L. Prospects for exosomes in immunotherapy of cancer. J Cell Mol Med. 2006;10:376–388. doi:10.1111/jcmm.2006.10.issue-216796806
   PubMed Web of Science ®Google Scholar
• Ohno H. Overview: membrane traffic in multicellular systems: more than just a housekeeper. J Biochem. 2006;139:941–942. doi:10.1093/jb/mvj11916788043
   PubMed Web of Science ®Google Scholar
• Wada J, Onishi H, Suzuki H, et al. Surface-bound TGF-beta1 on effusion-derived exosomes participates in maintenance of number and suppressive function of regulatory T-cells in malignant effusions. Anticancer Res. 2010;30:3747–3757.20944164
   PubMed Web of Science ®Google Scholar
• Onishi H, Morisaki T, Katano M. Immunotherapy approaches targeting regulatory T-cells. Anticancer Res. 2012;32:997–1003.22399623
   PubMed Web of Science ®Google Scholar
• Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol. 2009;155:173–181. doi:10.1111/cei.2009.155.issue-219128359
   PubMed Web of Science ®Google Scholar
• Tree TI, Roep BO, Peakman M. A mini meta-analysis of studies on CD4+CD25+ T cells in human type 1 diabetes: report of the immunology of diabetes society T cell workshop. Ann N Y Acad Sci. 2006;1079:9–18. doi:10.1196/annals.1375.00217130526
   PubMed Web of Science ®Google Scholar
• Izcue A, Powrie F. Special regulatory T-cell review: regulatory T cells and the intestinal tract–patrolling the frontier. Immunology. 2008;123:6–10. doi:10.1111/imm.2008.123.issue-118154611
   PubMed Web of Science ®Google Scholar
• Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057–1061. doi:10.1126/science.107949012522256
   PubMed Web of Science ®Google Scholar
• Kohm AP, Carpentier PA, Anger HA, Miller SD. Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J Immunol. 2002;169:4712–4716. doi:10.4049/jimmunol.169.9.471212391178
   PubMed Web of Science ®Google Scholar
• Morgan ME, Sutmuller RP, Witteveen HJ, et al. CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis. Arthritis Rheum. 2003;48:1452–1460. doi:10.1002/art.1106312746920
   PubMed Web of Science ®Google Scholar
• Buckner JH. Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases. Nat Rev Immunol. 2010;10:849–859. doi:10.1038/nri288921107346
   PubMed Web of Science ®Google Scholar
• Yan KX, Fang X, Han L, et al. Foxp3+ regulatory T cells and related cytokines differentially expressed in plaque vs. guttate psoriasis vulgaris. Br J Dermatol. 2010;163:48–56. doi:10.1111/j.1365-2133.2010.09742.x20222932
   PubMed Web of Science ®Google Scholar
• Bovenschen HJ, van Vlijmen-willems IM, van de Kerkhof PC, van Erp PE. Identification of lesional CD4+ CD25+ Foxp3+ regulatory T cells in Psoriasis. Dermatology. 2006;213:111–117. doi:10.1159/00009384916902287
   PubMed Web of Science ®Google Scholar
• Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat Rev Immunol. 2003;3:199–210. doi:10.1038/nri102712658268
   PubMed Web of Science ®Google Scholar
• Cohen JL, Trenado A, Vasey D, Klatzmann D, Salomon BL. CD4(+)CD25(+) immunoregulatory T cells: new therapeutics for graft-versus-host disease. J Exp Med. 2002;196:401–406. doi:10.1084/jem.2002009012163568
   PubMed Web of Science ®Google Scholar
• Edinger M, Hoffmann P, Ermann J, et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med. 2003;9:1144–1150. doi:10.1038/nm91512925844
   PubMed Web of Science ®Google Scholar
• Taylor PA, Lees CJ, Blazar BR. The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood. 2002;99:3493–3499. doi:10.1182/blood.V99.10.349311986199
   PubMed Web of Science ®Google Scholar
• Gallimore A, Sakaguchi S. Regulation of tumour immunity by CD25+ T cells. Immunology. 2002;107:5–9. doi:10.1046/j.1365-2567.2002.01471.x12225357
   PubMed Web of Science ®Google Scholar
• Zenclussen AC. CD4(+)CD25+ T regulatory cells in murine pregnancy. J Reprod Immunol. 2005;65:101–110. doi:10.1016/j.jri.2005.01.00315811515
   PubMed Web of Science ®Google Scholar
• Maj T, Wang W, Crespo J, et al. Oxidative stress controls regulatory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor. Nat Immunol. 2017;18:1332–1341. doi:10.1038/ni.386829083399
   PubMed Web of Science ®Google Scholar
• Chung KY, Gore I, Fong L, et al. Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer. J Clin Oncol. 2010;28:3485–3490. doi:10.1200/JCO.2010.28.399420498386
   PubMed Web of Science ®Google Scholar
• Ralph C, Elkord E, Burt DJ, et al. Modulation of lymphocyte regulation for cancer therapy: a phase II trial of tremelimumab in advanced gastric and esophageal adenocarcinoma. Clin Cancer Res. 2010;16:1662–1672. doi:10.1158/1078-0432.CCR-09-287020179239
   PubMed Web of Science ®Google Scholar
• Kirkwood JM, Lorigan P, Hersey P, et al. Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma. Clin Cancer Res. 2010;16:1042–1048. doi:10.1158/1078-0432.CCR-09-203320086001
   PubMed Web of Science ®Google Scholar
• Camacho LH, Antonia S, Sosman J, et al. Phase I/II trial of tremelimumab in patients with metastatic melanoma. J Clin Oncol. 2009;27:1075–1081. doi:10.1200/JCO.2008.19.243519139427
   PubMed Web of Science ®Google Scholar
• Rech AJ, Vonderheide RH. Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells. Ann N Y Acad Sci. 2009;1174:99–106. doi:10.1111/j.1749-6632.2009.04939.x19769742
   PubMed Web of Science ®Google Scholar
• Mahnke K, Schonfeld K, Fondel S, et al. 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. 2007;120:2723–2733. doi:10.1002/ijc.2261717315189
   PubMed Web of Science ®Google Scholar
• Powell DJ Jr., Felipe-Silva A, Merino MJ, et al. Administration of a CD25-directed immunotoxin, LMB-2, to patients with metastatic melanoma induces a selective partial reduction in regulatory T cells in vivo. J Immunol. 2007;179:4919–4928. doi:10.4049/jimmunol.179.7.491917878392
   PubMed Web of Science ®Google Scholar
• Curtin JF, Candolfi M, Fakhouri TM, et al. Treg depletion inhibits efficacy of cancer immunotherapy: implications for clinical trials. PLoS One. 2008;3:e1983. doi:10.1371/journal.pone.000198318431473
   PubMed Web of Science ®Google Scholar
• Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21 ):2018–2028. doi:10.1056/NEJMoa150182425891174
   PubMed Web of Science ®Google Scholar
• Oberst MD, Augé C, Morris C, et al. Potent immune modulation by MEDI6383, an engineered human OX40 ligand IgG4P Fc fusion protein. Mol Cancer Ther. 2018;17(5 ):1024–1038. doi:10.1158/1535-7163.MCT-17-020029545330
   PubMed Web of Science ®Google Scholar
• Preston CC, Goode EL, Hartmann LC, Kalli KR, Knutson KL. Immunity and immune suppression in human ovarian cancer. Immunotherapy. 2011;3:539–556. doi:10.2217/imt.11.2021463194
   PubMed Web of Science ®Google Scholar
• Maker AV, Phan GQ, Attia P, et al. Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann Surg Oncol. 2005;12:1005–1016. doi:10.1245/ASO.2005.03.53616283570
   PubMed Web of Science ®Google Scholar