Microbial metabolite butyrate promotes anti-PD-1 antitumor efficacy by modulating T cell receptor signaling of cytotoxic CD8 T cell

References

• Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, Lebbe C, Baurain J-F, Testori A, Grob J-J, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517–19. doi:10.1056/NEJMoa1104621.
   PubMed Web of Science ®Google Scholar
• Hiam-Galvez KJ, Allen BM, Spitzer MH. Systemic immunity in cancer. Nat Rev Cancer. 2021;21(6):345–359. doi:10.1038/s41568-021-00347-z.
   PubMed Web of Science ®Google Scholar
• Kraehenbuehl L, Weng CH, Eghbali S, Wolchok JD, Merghoub T. Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways. Nat Rev Clin Oncol. 2022;19(1):37–50. doi:10.1038/s41571-021-00552-7.
   PubMed Web of Science ®Google Scholar
• Chow A, Perica K, Klebanoff CA, Wolchok JD. Clinical implications of T cell exhaustion for cancer immunotherapy. Nat Rev Clin Oncol. 2022;19(12):775–790. doi:10.1038/s41571-022-00689-z.
   PubMed Web of Science ®Google Scholar
• Kim TK, Vandsemb EN, Herbst RS, Chen L. Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities. Nat Rev Drug Discov. 2022;21(7):529–540. doi:10.1038/s41573-022-00493-5.
   PubMed Web of Science ®Google Scholar
• Li P, Zhu X, Cao G, Wu R, Li K, Yuan W, Chen B, Sun G, Xia X, Zhang H, et al. 1α,25(OH)2D3 reverses exhaustion and enhances antitumor immunity of human cytotoxic T cells. J Immunother Cancer. 2022;10(3):10. doi:10.1136/jitc-2021-003477.
   Web of Science ®Google Scholar
• He X, Xu C. Immune checkpoint signaling and cancer immunotherapy. Cell Res. 2020;30(8):660–669. doi:10.1038/s41422-020-0343-4.
   PubMed Web of Science ®Google Scholar
• Havel JJ, Chowell D, Chan TA. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer. 2019;19(3):133–150. doi:10.1038/s41568-019-0116-x.
   PubMed Web of Science ®Google Scholar
• Sanmamed MF, Chen L. A paradigm shift in cancer immunotherapy: From enhancement to normalization. Cell. 2018;175(2):313–326. doi:10.1016/j.cell.2018.09.035.
   PubMed Web of Science ®Google Scholar
• de Vries NL, van de Haar J, Veninga V, Chalabi M, Ijsselsteijn ME, van der Ploeg M, van den Bulk J, Ruano D, van den Berg JG, Haanen JB, et al. γδ T cells are effectors of immunotherapy in cancers with HLA class I defects. Nature. 2023;613(7945):743–750. doi:10.1038/s41586-022-05593-1.
   PubMed Web of Science ®Google Scholar
• Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Sci. 2011;331(6024):1565–1570. doi:10.1126/science.1203486.
   PubMed Web of Science ®Google Scholar
• Sebestyen Z, Prinz I, Dechanet-Merville J, Silva-Santos B, Kuball J. Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies. Nat Rev Drug Discov. 2020;19(3):169–184. doi:10.1038/s41573-019-0038-z.
   PubMed Web of Science ®Google Scholar
• Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, Molina DA, Salcedo R, Back T, Cramer S, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013;342(6161):967–970. doi:10.1126/science.1240527.
   PubMed Web of Science ®Google Scholar
• Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF. The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients. Science. 2018;359(6371):104–108. doi:10.1126/science.aao3290.
   PubMed Web of Science ®Google Scholar
• Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. 2018;359(6371):91–97. doi:10.1126/science.aan3706.
   PubMed Web of Science ®Google Scholar
• Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, Flament C, Rusakiewicz S, Routy B, Roberti MP, Duong CPM, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079–1084. doi:10.1126/science.aad1329.
   PubMed Web of Science ®Google Scholar
• Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Man Lei Y, Jabri B, Alegre M-L, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science. 2015;350(6264):1084–1089. doi:10.1126/science.aac4255.
   PubMed Web of Science ®Google Scholar
• Lu Y, Yuan X, Wang M, He Z, Li H, Wang J, Li Q. Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies. J Hematol Oncol. 2022;15(1):47. doi:10.1186/s13045-022-01273-9.
   PubMed Web of Science ®Google Scholar
• Derosa L, Routy B, Thomas AM, Iebba V, Zalcman G, Friard S, Mazieres J, Audigier-Valette C, Moro-Sibilot D, Goldwasser F, et al. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer. Nat Med. 2022;28(2):315–324. doi:10.1038/s41591-021-01655-5.
   PubMed Web of Science ®Google Scholar
• Zhang SL, Han B, Mao YQ, Zhang ZY, Li ZM, Kong CY, Wu Y, Chen G-Q, Wang L-S. Lacticaseibacillus paracasei sh2020 induced antitumor immunity and synergized with anti-programmed cell death 1 to reduce tumor burden in mice. Gut Microbes. 2022;14(1):2046246. doi:10.1080/19490976.2022.2046246.
   PubMed Web of Science ®Google Scholar
• Wang L, Tang L, Zhai D, Song M, Li W, Xu S, Jiang S, Meng H, Liang J, Wang Y, et al. The role of the sex hormone-gut microbiome axis in tumor immunotherapy. Gut Microbes. 2023;15(1):2185035. doi:10.1080/19490976.2023.2185035.
   PubMed Web of Science ®Google Scholar
• Zitvogel L, Ma Y, Raoult D, Kroemer G, Gajewski TF. The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies. Science. 2018;359(6382):1366–1370. doi:10.1126/science.aar6918.
   PubMed Web of Science ®Google Scholar
• Baruch EN, Wang J, Wargo JA. Gut microbiota and antitumor immunity: Potential mechanisms for clinical effect. Cancer Immunol Res. 2021;9(4):365–370. doi:10.1158/2326-6066.CIR-20-0877.
   PubMed Web of Science ®Google Scholar
• Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut. 1987;28(10):1221–1227. doi:10.1136/gut.28.10.1221.
   PubMed Web of Science ®Google Scholar
• Sprouse ML, Bates NA, Felix KM, Wu HJ. Impact of gut microbiota on gut-distal autoimmunity: a focus on T cells. Immunology. 2019;156(4):305–318. doi:10.1111/imm.13037.
   PubMed Web of Science ®Google Scholar
• He Y, Fu L, Li Y, Wang W, Gong M, Zhang J, Dong X, Huang J, Wang Q, Mackay CR, et al. Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity. Cell Metab. 2021;33(5):988–1000.e7. doi:10.1016/j.cmet.2021.03.002.
   PubMed Web of Science ®Google Scholar
• Luu M, Riester Z, Baldrich A, Reichardt N, Yuille S, Busetti A, Klein M, Wempe A, Leister H, Raifer H, et al. Microbial short-chain fatty acids modulate CD8(+) T cell responses and improve adoptive immunotherapy for cancer. Nat Commun. 2021;12(1):4077. doi:10.1038/s41467-021-24331-1.
   PubMed Web of Science ®Google Scholar
• Danne C, Sokol H. Butyrate, a new microbiota-dependent player in CD8+ T cells immunity and cancer therapy? Cell Rep Med. 2021;2(7):100328. doi:10.1016/j.xcrm.2021.100328.
   PubMedGoogle Scholar
• Rangan P, Mondino A. Microbial short-chain fatty acids: a strategy to tune adoptive T cell therapy. J Immunother Cancer. 2022;10(7):10. doi:10.1136/jitc-2021-004147.
   Web of Science ®Google Scholar
• Nomura M, Nagatomo R, Doi K, Shimizu J, Baba K, Saito T, Matsumoto S, Inoue K, Muto M. Association of Short-chain fatty acids in the gut microbiome with clinical response to treatment with Nivolumab or Pembrolizumab in patients with solid cancer tumors. JAMA Network Open. 2020;3(4):e202895. doi:10.1001/jamanetworkopen.2020.2895.
   PubMed Web of Science ®Google Scholar
• Li P, Wu R, Li K, Yuan W, Zeng C, Zhang Y, Wang X, Zhu X, Zhou J, Li P, et al. IDO inhibition facilitates antitumor immunity of Vγ9Vδ2 T cells in Triple-Negative Breast cancer. Front Oncol. 2021;11:679517. doi:10.3389/fonc.2021.679517.
   PubMed Web of Science ®Google Scholar
• Kamphorst AO, Wieland A, Nasti T, Yang S, Zhang R, Barber DL, Konieczny BT, Daugherty CZ, Koenig L, Yu K, et al. Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent. Science. 2017;355(6332):1423–1427. doi:10.1126/science.aaf0683.
   PubMed Web of Science ®Google Scholar
• Hui E, Cheung J, Zhu J, Su X, Taylor MJ, Wallweber HA, Sasmal DK, Huang J, Kim JM, Mellman I, et al. T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition. Science. 2017;355(6332):1428–1433. doi:10.1126/science.aaf1292.
   PubMed Web of Science ®Google Scholar
• Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504(7480):446–450. doi:10.1038/nature12721.
   PubMed Web of Science ®Google Scholar
• Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451–455. doi:10.1038/nature12726.
   PubMed Web of Science ®Google Scholar
• Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly YM, Glickman JN, Garrett WS. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569–573. doi:10.1126/science.1241165.
   PubMed Web of Science ®Google Scholar
• Trebak M, Kinet JP. Calcium signalling in T cells. Nat Rev Immunol. 2019;19(3):154–169. doi:10.1038/s41577-018-0110-7.
   PubMed Web of Science ®Google Scholar
• Morad G, Helmink BA, Sharma P, Wargo JA. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell. 2021;184(21):5309–5337. doi:10.1016/j.cell.2021.09.020.
   PubMed Web of Science ®Google Scholar
• Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, et al. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97–103. doi:10.1126/science.aan4236.
   PubMed Web of Science ®Google Scholar
• Ahern PP, Maloy KJ. Understanding immune–microbiota interactions in the intestine. Immunology. 2020;159(1):4–14. doi:10.1111/imm.13150.
   PubMed Web of Science ®Google Scholar
• Park J, Kim M, Kang SG, Jannasch AH, Cooper B, Patterson J, Kim CH. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR–S6K pathway. Mucosal Immunol. 2015;8(1):80–93. doi:10.1038/mi.2014.44.
   PubMed Web of Science ®Google Scholar
• Kroemer G, McQuade JL, Merad M, Andre F, Zitvogel L. Bodywide ecological interventions on cancer. Nat Med. 2023;29(1):59–74. doi:10.1038/s41591-022-02193-4.
   PubMedGoogle Scholar
• Kamphorst AO, Wieland A, Nasti T, Yang S, Zhang R, Barber DL, Konieczny BT, Daugherty CZ, Koenig L, Yu K, et al. Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent. Science. 2017;355(6332):1423–1427. doi:10.1126/science.aaf0683.
   PubMed Web of Science ®Google Scholar
• Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13(4):227–242. doi:10.1038/nri3405.
   PubMed Web of Science ®Google Scholar
• Yang W, Pan W, Chen S, Trendel N, Jiang S, Xiao F, Xue M, Wu W, Peng Z, Li X, et al. Dynamic regulation of CD28 conformation and signaling by charged lipids and ions. Nature Structural & Molecular Biology. 2017;24(12):1081–1092. doi:10.1038/nsmb.3489.
   PubMed Web of Science ®Google Scholar
• Abraham RT, Weiss A. Jurkat T cells and development of the T-cell receptor signalling paradigm. Nat Rev Immunol. 2004;4(4):301–308. doi:10.1038/nri1330.
   PubMed Web of Science ®Google Scholar
• von Essen MR, Kongsbak M, Schjerling P, Olgaard K, Odum N, Geisler C. Vitamin D controls T cell antigen receptor signaling and activation of human T cells. Nat Immunol. 2010;11(4):344–349. doi:10.1038/ni.1851.
   PubMed Web of Science ®Google Scholar
• Liang W, Yi R, Wang W, Shi Y, Zhang J, Xu X, Wang Q, Liu M, Wang F. Enhancing the antitumor immunity of T cells by Engineering the Lipid-regulatory Site of the TCR/CD3 complex. Cancer Immunol Res. 2023;11(1):93–108. doi:10.1158/2326-6066.CIR-21-1118.
   PubMed Web of Science ®Google Scholar
• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–247. doi:10.1016/j.ejca.2008.10.026.
   PubMed Web of Science ®Google Scholar