Autophagy Regulation of Metabolism Is Required for CD8+ T Cell Anti-tumor Immunity

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dc.contributor.authorDeVorkin, Lindsay
dc.contributor.authorPavey, Nils
dc.contributor.authorCarleton, Gillian
dc.contributor.authorComber, Alexandra
dc.contributor.authorHo, Cally
dc.contributor.authorLim, Junghyun
dc.contributor.authorMcNamara, Erin
dc.contributor.authorHuang, Haochu
dc.contributor.authorKim, Paul
dc.contributor.authorZacharias, Lauren G.
dc.contributor.authorMizushima, Noboru
dc.contributor.authorSaitoh, Tatsuya
dc.contributor.authorAkira, Shizuo
dc.contributor.authorBeckham, Wayne
dc.contributor.authorLorzadeh, Alireza
dc.contributor.authorMoksa, Michelle
dc.contributor.authorCao, Qi
dc.contributor.authorMurthy, Aditya
dc.contributor.authorHirst, Martin
dc.contributor.authorDeBerardinis, Ralph J.
dc.contributor.authorLum, Julian J.
dc.date.accessioned2019-05-03T12:33:41Z
dc.date.available2019-05-03T12:33:41Z
dc.date.copyright2019en_US
dc.date.issued2019
dc.description.abstractAutophagy is a cell survival process essential for the regulation of immune responses to infections. However, the role of T cell autophagy in anti-tumor immunity is less clear. Here, we demonstrate a cell-autonomous role for autophagy in the regulation of CD8+ T-cell-mediated control of tumors. Mice deficient for the essential autophagy genes Atg5, Atg14, or Atg16L1 display a dramatic impairment in the growth of syngeneic tumors. Moreover, T cells lacking Atg5 have a profound shift to an effector memory phenotype and produce greater amounts of interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α). Mechanistically, Atg5−/− CD8+ T cells exhibit enhanced glucose metabolism that results in alterations in histone methylation, increases in H3K4me3 density, and transcriptional upregulation of both metabolic and effector target genes. Nonetheless, glucose restriction is sufficient to suppress Atg5-dependent increases in effector function. Thus, autophagy-dependent changes in CD8+ T cell metabolism directly regulate anti-tumor immunity.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis study was supported by the Canadian Breast Cancer Foundation (J.J.L.), the BC Cancer Foundation (J.J.L.), the Canadian Breast Cancer Foundation Fellowship (L.D.), the Howard Hughes Medical Institute (Faculty Scholars Program; R.J.D.), and the National Cancer Institute (1R35CA22044901; R.J.D.).en_US
dc.identifier.citationDeVorkin, L., Pavey, N., Carleton, G., Comber, A., Ho, C., Lim, J. & Lum, J.J. (2019). Autophagy Regulation of Metabolism Is Required for CD8+ T Cell Antitumor Immunity. Cell Reports, 27(2), 502-513.e5. https://doi.org/10.1016/j.celrep.2019.03.037en_US
dc.identifier.urihttps://doi.org/10.1016/j.celrep.2019.03.037
dc.identifier.urihttp://hdl.handle.net/1828/10840
dc.language.isoenen_US
dc.publisherCell Reportsen_US
dc.subject.departmentDepartment of Biochemistry and Microbiology
dc.subject.departmentDepartment of Physics and Astronomy
dc.titleAutophagy Regulation of Metabolism Is Required for CD8+ T Cell Anti-tumor Immunityen_US
dc.typeArticleen_US

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