Regulatory T cells (Tregs): A major immune checkpoint to consider in combinatorial therapeutic HIV-1 vaccines

References

• Pantaleo G, Levy Y. Therapeutic vaccines and immunological intervention in HIV infection: a paradigm change. Curr Opin HIV AIDS. 2016;11:576-84. doi:10.1097/COH.0000000000000324. PMID:27607591.
   PubMed Web of Science ®Google Scholar
• Seddiki N, Brezar V, Draenert R. Cell exhaustion in HIV-1 infection: role of suppressor cells. Curr Opin HIV AIDS. 2014;9:452-8. doi:10.1097/COH.0000000000000087. PMID:25010895.
   PubMed Web of Science ®Google Scholar
• Welters MJ, Kenter GG, de Vos van Steenwijk PJ, Lowik MJ, Berends-van der Meer DM, Essahsah F, Stynenbosch LF, Vloon AP, Ramwadhdoebe TH, Piersma SJ. Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses. Proc Natl Acad Sci U S A. 2010;107:11895-9. doi:10.1073/pnas.1006500107. PMID:20547850.
   PubMed Web of Science ®Google Scholar
• Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, Ezoe S, Kanakura Y, Sato E, Fukumori Y. Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. Proc Natl Acad Sci U S A. 2013;110:17945-50. doi:10.1073/pnas.1316796110. PMID:24127572.
   PubMed Web of Science ®Google Scholar
• Simonetta F, Bourgeois C. CD4+FOXP3+ Regulatory T-Cell Subsets in human immunodeficiency virus infection. Front Immunol. 2013;4:215. doi:10.3389/fimmu.2013.00215. PMID:23908654.
   PubMed Web of Science ®Google Scholar
• Brezar V, Hani L, Surenaud M, Hubert A, Lacabaratz C, Lelievre JD, Levy Y, Seddiki N. Negative modulation of suppressive HIV-specific regulatory T cells by IL-2 adjuvanted therapeutic vaccine. PLoS Pathog. 2017;13:e1006489. doi:10.1371/journal.ppat.1006489. PMID:28708863.
   PubMed Web of Science ®Google Scholar
• Wykes MN, Lewin SR. Immune checkpoint blockade in infectious diseases. Nat Rev Immunol. 2017;18:91–104. doi:10.1038/nri.2017.112. PMID:28990586.
   PubMed Web of Science ®Google Scholar
• Apostolopoulos V, Marincola FM. Methods to measure vaccine immunity. Expert Rev Vaccines. 2010;9:545-6. doi:10.1586/erv.10.61. PMID:20518709.
   PubMed Web of Science ®Google Scholar
• Brezar V, Godot V, Cheng L, Su L, Levy Y, Seddiki N. T-regulatory cells and vaccination “pay attention and do not neglect them”: lessons from hiv and cancer vaccine trials. Vaccines (Basel). 2016;4:1–13. doi:10.3390/vaccines4030030. PMID:27608046.
   PubMed Web of Science ®Google Scholar
• Zaunders JJ, Munier ML, Seddiki N, Pett S, Ip S, Bailey M, Xu Y, Brown K, Dyer WB, Kim M. High levels of human antigen-specific CD4+ T cells in peripheral blood revealed by stimulated coexpression of CD25 and CD134 (OX40). J Immunol. 2009;183:2827-36. doi:10.4049/jimmunol.0803548. PMID:19635903.
   PubMed Web of Science ®Google Scholar
• Seddiki N, Cook L, Hsu DC, Phetsouphanh C, Brown K, Xu Y, Xu Y, Kerr SJ, Cooper DA, Munier CM, Pett S. Human antigen-specific CD4(+) CD25(+) CD134(+) CD39(+) T cells are enriched for regulatory T cells and comprise a substantial proportion of recall responses. Eur J Immunol. 2014;44:1644-61. doi:10.1002/eji.201344102. PMID:24752698.
   PubMed Web of Science ®Google Scholar
• Havenar-Daughton C, Reiss SM, Carnathan DG, Wu JE, Kendric K, Torrents de la Pena A, Kasturi SP, Dan JM, Bothwell M, Sanders RW. Cytokine-independent detection of antigen-specific germinal center t follicular helper cells in immunized nonhuman primates using a live cell activation-induced marker technique. J Immunol. 2016;197:994-1002. doi:10.4049/jimmunol.1600320. PMID:27335502.
   PubMed Web of Science ®Google Scholar
• Dan JM, Lindestam Arlehamn CS, Weiskopf D, da Silva Antunes R, Havenar-Daughton C, Reiss SM, et al. A cytokine-independent approach to identify antigen-specific human germinal center t follicular helper cells and rare antigen-specific CD4+ T cells in blood. J Immunol. 2016;197:983-93. doi:10.4049/jimmunol.1600318. PMID:27342848.
   PubMed Web of Science ®Google Scholar
• Reiss S, Baxter AE, Cirelli KM, Dan JM, Morou A, Daigneault A, Brassard N, Silvestri G, Routy JP, Havenar-Daughton C. Comparative analysis of activation induced marker (AIM) assays for sensitive identification of antigen-specific CD4 T cells. PLoS One. 2017;12:e0186998. doi:10.1371/journal.pone.0186998. PMID:29065175.
   PubMed Web of Science ®Google Scholar
• Brezar V, Ruffin N, Richert L, Surenaud M, Lacabaratz C, Palucka K, Thiébaut R, Banchereau J, Levy Y, Seddiki N. Decreased HIV-specific T-regulatory responses are associated with effective DC-vaccine induced immunity. PLoS Pathog. 2015;11:e1004752. doi:10.1371/journal.ppat.1004752. PMID:25816350.
   PubMed Web of Science ®Google Scholar
• Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252-64. doi:10.1038/nrc3239. PMID:22437870.
   PubMed Web of Science ®Google Scholar
• Gay CL, Bosch RJ, Ritz J, Hataye JM, Aga E, Tressler RL, Mason SW, Hwang CK, Grasela DM, Ray N. Clinical Trial of the Anti-PD-L1 Antibody BMS-936559 in HIV-1 infected participants on suppressive antiretroviral therapy. J Infect Dis. 2017;215:1725-33. doi:10.1093/infdis/jix191. PMID:28431010.
   PubMed Web of Science ®Google Scholar
• Velu V, Titanji K, Zhu B, Husain S, Pladevega A, Lai L, Vanderford TH, Chennareddi L, Silvestri G, Freeman GJ. Enhancing SIV-specific immunity in vivo by PD-1 blockade. Nature. 2009;458:206-10. doi:10.1038/nature07662. PMID:19078956.
   PubMed Web of Science ®Google Scholar
• Toor SM, Syed Khaja AS, Alkurd I, Elkord E. In-vitro effect of pembrolizumab on different T regulatory cell subsets. Clin Exp Immunol. 2018;191:189-97. doi:10.1111/cei.13060. PMID:28963773.
   PubMed Web of Science ®Google Scholar
• West EE, Jin HT, Rasheed AU, Penaloza-Macmaster P, Ha SJ, Tan WG, Youngblood B, Freeman GJ, Smith KA, Ahmed R. PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. J Clin Invest. 2013;123:2604-15. doi:10.1172/JCI67008. PMID:23676462.
   PubMed Web of Science ®Google Scholar
• Moynihan KD, Opel CF, Szeto GL, Tzeng A, Zhu EF, Engreitz JM, Williams RT, Rakhra K, Zhang MH, Rothschilds AM. Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Nat Med. 2016;22:1402-10. doi:10.1038/nm.4200. PMID:27775706.
   PubMed Web of Science ®Google Scholar
• Levy Y, Capitant C, Houhou S, Carriere I, Viard JP, Goujard C, et al. Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: A randomised controlled trial. ANRS 048 study group. Lancet. 1999;353:1923-9. doi:10.1016/S0140-6736(98)07345-0. PMID:10371571.
   PubMed Web of Science ®Google Scholar
• Group I-ES, Committee SS, Abrams D, Levy Y, Losso MH, Babiker A, Collins G, Cooper DA, Darbyshire J, Emery S. Interleukin-2 therapy in patients with HIV infection. N Engl J Med. 2009;361:1548-59. doi:10.1056/NEJMoa0903175. PMID:19828532.
   PubMed Web of Science ®Google Scholar
• Weiss L, Letimier FA, Carriere M, Maiella S, Donkova-Petrini V, Targat B, Benecke A, Rogge L, Levy Y. In vivo expansion of naive and activated CD4+CD25+FOXP3+ regulatory T cell populations in interleukin-2-treated HIV patients. Proc Natl Acad Sci U S A. 2010;107:10632-7. doi:10.1073/pnas.1000027107. PMID:20498045.
   PubMed Web of Science ®Google Scholar
• Beq S, Nugeyre MT, Ho Tsong Fang R, Gautier D, Legrand R, Schmitt N, et al. IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy. J Immunol. 2006;176:914-22. doi:10.4049/jimmunol.176.2.914. PMID:16393976.
   PubMed Web of Science ®Google Scholar
• Sereti I, Dunham RM, Spritzler J, Aga E, Proschan MA, Medvik K, Battaglia CA, Landay AL, Pahwa S, Fischl MA. IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Blood. 2009;113:6304-14. doi:10.1182/blood-2008-10-186601. PMID:19380868.
   PubMed Web of Science ®Google Scholar
• Sereti I, Estes JD, Thompson WL, Morcock DR, Fischl MA, Croughs T, Beq S, Lafaye de Micheaux S, Yao MD, Ober A. Decreases in colonic and systemic inflammation in chronic HIV infection after IL-7 administration. PLoS Pathog. 2014;10:e1003890. doi:10.1371/journal.ppat.1003890. PMID:24497828.
   PubMed Web of Science ®Google Scholar
• Levy Y, Lacabaratz C, Weiss L, Viard JP, Goujard C, Lelievre JD, Boué F, Molina JM, Rouzioux C, Avettand-Fénoêl V. Enhanced T cell recovery in HIV-1-infected adults through IL-7 treatment. J Clin Invest. 2009;119:997-1007. PMID:19287090.
   PubMed Web of Science ®Google Scholar
• Thiebaut R, Jarne A, Routy JP, Sereti I, Fischl M, Ive P, Speck RF, D'Offizi G, Casari S, Commenges D. Repeated Cycles of Recombinant Human Interleukin 7 in HIV-Infected Patients With Low CD4 T-Cell Reconstitution on Antiretroviral Therapy: Results of 2 Phase II Multicenter Studies. Clin Infect Dis. 2016;62:1178-85. doi:10.1093/cid/ciw065. PMID:26908786.
   PubMed Web of Science ®Google Scholar
• Younas M, Hue S, Lacabaratz C, Guguin A, Wiedemann A, Surenaud M, et al. IL-7 modulates in vitro and in vivo human memory T regulatory cell functions through the CD39/ATP axis. J Immunol. 2013;191:3161-8. doi:10.4049/jimmunol.1203547. PMID:23966629.
   PubMed Web of Science ®Google Scholar
• Levy Y, Sereti I, Tambussi G, Routy JP, Lelievre JD, Delfraissy JF, Molina JM, Fischl M, Goujard C, Rodriguez B. Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebo-controlled, multicenter study. Clin Infect Dis. 2012;55:291-300. doi:10.1093/cid/cis383. PMID:22550117.
   PubMed Web of Science ®Google Scholar
• Katlama C, Lambert-Niclot S, Assoumou L, Papagno L, Lecardonnel F, Zoorob R, Tambussi G, Clotet B, Youle M, Achenbach CJ. Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial. AIDS. 2016;30:221-30. doi:10.1097/QAD.0000000000000894. PMID:26684819.
   PubMed Web of Science ®Google Scholar
• Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, Boucher G, Boulassel MR, Ghattas G, Brenchley JM. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009;15:893-900. doi:10.1038/nm.1972. PMID:19543283.
   PubMed Web of Science ®Google Scholar
• Grabstein KH, Eisenman J, Shanebeck K, Rauch C, Srinivasan S, Fung V, Beers C, Richardson J, Schoenborn MA, Ahdieh M. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science. 1994;264:965-8. doi:10.1126/science.8178155. PMID:8178155.
   PubMed Web of Science ®Google Scholar
• Hasan AN, Selvakumar A, Shabrova E, Liu XR, Afridi F, Heller G, Riviere I, Sadelain M, Dupont B, O'Reilly RJ. Soluble and membrane-bound interleukin (IL)-15 Ralpha/IL-15 complexes mediate proliferation of high-avidity central memory CD8(+) T cells for adoptive immunotherapy of cancer and infections. Clin Exp Immunol. 2016;186:249-65. doi:10.1111/cei.12816. PMID:27227483.
   PubMed Web of Science ®Google Scholar
• Van den Bergh JMJ, Smits E, Berneman ZN, Hutten TJA, De Reu H, Van Tendeloo VFI, Dolstra H, Lion E, Hobo W. Monocyte-derived dendritic cells with silenced PD-1 ligands and transpresenting interleukin-15 stimulate strong tumor-reactive t-cell expansion. Cancer Immunol Res. 2017;5:710-5. doi:10.1158/2326-6066.CIR-16-0336. PMID:28637876.
   PubMed Web of Science ®Google Scholar
• Seay K, Church C, Zheng JH, Deneroff K, Ochsenbauer C, Kappes JC, Liu B, Jeng EK, Wong HC, Goldstein H. In Vivo Activation of Human NK Cells by Treatment with an Interleukin-15 Superagonist Potently Inhibits Acute In Vivo HIV-1 Infection in Humanized Mice. J Virol. 2015;89:6264-74. doi:10.1128/JVI.00563-15. PMID:25833053.
   PubMed Web of Science ®Google Scholar
• Guo Y, Luan L, Patil NK, Sherwood ER. Immunobiology of the IL-15/IL-15Ralpha complex as an antitumor and antiviral agent. Cytokine Growth Factor Rev. 2017;38:10-21. doi:10.1016/j.cytogfr.2017.08.002. PMID:28888485.
   PubMed Web of Science ®Google Scholar
• Mathios D, Park CK, Marcus WD, Alter S, Rhode PR, Jeng EK, Wong HC, Pardoll DM, Lim M. Therapeutic administration of IL-15 superagonist complex ALT-803 leads to long-term survival and durable antitumor immune response in a murine glioblastoma model. Int J Cancer. 2016;138:187-94. doi:10.1002/ijc.29686. PMID:26174883.
   PubMed Web of Science ®Google Scholar
• Kim PS, Kwilas AR, Xu W, Alter S, Jeng EK, Wong HC, Schlom J, Hodge JW. IL-15 superagonist/IL-15RalphaSushi-Fc fusion complex (IL-15SA/IL-15RalphaSu-Fc; ALT-803) markedly enhances specific subpopulations of NK and memory CD8+ T cells, and mediates potent anti-tumor activity against murine breast and colon carcinomas. Oncotarget. 2016;7:16130-45. PMID:26910920.
   PubMedGoogle Scholar
• Shang B, Liu Y, Jiang SJ, Liu Y. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis. Sci Rep. 2015;5:15179. doi:10.1038/srep15179. PMID:26462617.
   PubMed Web of Science ®Google Scholar
• Weiss L, Donkova-Petrini V, Caccavelli L, Balbo M, Carbonneil C, Levy Y. Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients. Blood. 2004;104:3249-56. doi:10.1182/blood-2004-01-0365. PMID:15271794.
   PubMed Web of Science ®Google Scholar
• Estes JD, Li Q, Reynolds MR, Wietgrefe S, Duan L, Schacker T, Picker LJ, Watkins DI, Lifson JD, Reilly C. Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection. J Infect Dis. 2006;193:703-12. doi:10.1086/500368. PMID:16453267.
   PubMed Web of Science ®Google Scholar
• Tenorio AR, Martinson J, Pollard D, Baum L, Landay A. The relationship of T-regulatory cell subsets to disease stage, immune activation, and pathogen-specific immunity in HIV infection. J Acquir Immune Defic Syndr. 2008;48:577-80. doi:10.1097/QAI.0b013e31817bbea5. PMID:18645514.
   PubMed Web of Science ®Google Scholar
• Li G, Nunoya JI, Cheng L, Reszka-Blanco N, Tsao LC, Jeffrey J, Su L. Regulatory T Cells Contribute to HIV-1 Reservoir Persistence in CD4+ T Cells through cyclic adenosine monophosphate-dependent mechanisms in humanized mice in vivo. J Infect Dis. 2017;216:1579-91. doi:10.1093/infdis/jix547. PMID:29045701.
   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.x. PMID:19769742.
   PubMed Web of Science ®Google Scholar
• Rech AJ, Mick R, Martin S, Recio A, Aqui NA, Powell DJ Jr., Colligon TA, Trosko JA, Leinbach LI, Pletcher CH. CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients. Sci Transl Med. 2012;4:134ra62. doi:10.1126/scitranslmed.3003330. PMID:22593175.
   PubMed Web of Science ®Google Scholar
• Arce Vargas F, Furness AJS, Solomon I, Joshi K, Mekkaoui L, Lesko MH, Miranda Rota E, Dahan R, Georgiou A, Sledzinska A. Fc-Optimized Anti-CD25 depletes tumor-infiltrating regulatory t cells and synergizes with PD-1 blockade to eradicate established tumors. Immunity. 2017;46:577-86. doi:10.1016/j.immuni.2017.03.013. PMID:28410988.
   PubMed Web of Science ®Google Scholar
• Grinberg-Bleyer Y, Oh H, Desrichard A, Bhatt DM, Caron R, Chan TA, Schmid RM, Klein U, Hayden MS, Ghosh S. NF-kappaB c-Rel is crucial for the regulatory t cell immune checkpoint in cancer. Cell. 2017;170:1096-108 e13. doi:10.1016/j.cell.2017.08.004.
   PubMed Web of Science ®Google Scholar
• Selby MJ, Engelhardt JJ, Quigley M, Henning KA, Chen T, Srinivasan M, Korman AJ. Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Cancer Immunol Res. 2013;1:32-42. doi:10.1158/2326-6066.CIR-13-0013. PMID:24777248.
   PubMed Web of Science ®Google Scholar
• Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F, Roddie C, Henry JY, Yagita H, Wolchok JD. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med. 2013;210:1695-710. doi:10.1084/jem.20130579. PMID:23897981.
   PubMed Web of Science ®Google Scholar
• Wasiuk A, Testa J, Weidlick J, Sisson C, Vitale L, Widger J, Crocker A, Thomas LJ, Goldstein J, Marsh HC. CD27-mediated regulatory t cell depletion and effector t cell costimulation both contribute to antitumor efficacy. J Immunol. 2017;199:4110-23. doi:10.4049/jimmunol.1700606. PMID:29109120.
   PubMed Web of Science ®Google Scholar
• Mo L, Chen Q, Zhang X, Shi X, Wei L, Zheng D, Li H, Gao J, Li J, Hu Z. Depletion of regulatory T cells by anti-ICOS antibody enhances anti-tumor immunity of tumor cell vaccine in prostate cancer. Vaccine. 2017;35:5932-8. doi:10.1016/j.vaccine.2017.08.093. PMID:28923424.
   PubMed Web of Science ®Google Scholar
• Bulliard Y, Jolicoeur R, Zhang J, Dranoff G, Wilson NS, Brogdon JL. OX40 engagement depletes intratumoral Tregs via activating FcgammaRs, leading to antitumor efficacy. Immunol Cell Biol. 2014;92:475-80. doi:10.1038/icb.2014.26. PMID:24732076.
   PubMed Web of Science ®Google Scholar