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

Lindsay DeVorkin; Nils Pavey; Gillian Carleton; Alexandra Comber; Cally Ho; Junghyun Lim; Erin McNamara; Haochu Huang; Paul Kim; Lauren G. Zacharias; Noboru Mizushima; Tatsuya Saitoh; Shizuo Akira; Wayne Beckham; Alireza Lorzadeh; Michelle Moksa; Qi Cao; Aditya Murthy; Martin Hirst; Ralph J. DeBerardinis; Julian J. Lum

doi:10.1016/j.celrep.2019.03.037

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

Lindsay DeVorkin, Nils Pavey, Gillian Carleton, Alexandra Comber, Cally Ho, Junghyun Lim, Erin McNamara, Haochu Huang, Paul Kim, Lauren G. Zacharias, Noboru Mizushima, Tatsuya Saitoh, Shizuo Akira, Wayne Beckham, Alireza Lorzadeh, Michelle Moksa, Qi Cao, Aditya Murthy, Martin Hirst, Ralph J. DeBerardinisJulian J. Lum

Résultat de recherche: Article › examen par les pairs

136 Citations (Scopus)

Résumé

DeVorkin et al. show that loss of autophagy enhances CD8 ⁺ T-cell-mediated rejection of tumors. Mechanistically, suppression of autophagy shifts T cells to a glycolytic phenotype and causes a reduction in S-adenosylmethionine. As a consequence, autophagy-deficient T cells transcriptionally reprogram immune response genes to an effector memory state.

Langue d'origine	English
Pages (de-à)	502-513.e5
Journal	Cell Reports
Volume	27
Numéro de publication	2
DOI	https://doi.org/10.1016/j.celrep.2019.03.037
Statut de publication	Published - avr. 9 2019
Publié à l'externe	Oui

Note bibliographique

Funding Information:
The authors would like to thank Chris Johnstone and Dr. Magdalena Bazalova-Carter for assistance with radiation of mice to create the bone marrow chimeras, Dr. John Stagg for the e0771 cells, and Dr. Ravi Amaravadi for Lys05. This 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.). Conceptualization, L.D. and J.J.L.; Methodology, L.D. N.P. M.H. A.M. and J.J.L.; Investigation, L.D. N.P. G.C. A.C. C.H. P.K. J.L. E.M, H.H, L.G.Z. N.M. T.S. S.A. W.B. A.L. M.M. and Q.C.; Writing – Original Draft and Revisions, all authors; Visualization, L.D. A.C. and J.J.L. Supervision, L.D, A.M. M.H. and J.J.L. Funding Acquisition, L.D and J.J.L. R.J.D. is member of the Scientific Advisory Board at Agios Pharmaceuticals. A.M. J.L. E.M. and H.H. are employees of Genentech Inc. L.D. and J.J.L. are named inventors on a provisional patent related to the research in this manuscript.

Funding Information:
The authors would like to thank Chris Johnstone and Dr. Magdalena Bazalova-Carter for assistance with radiation of mice to create the bone marrow chimeras, Dr. John Stagg for the e0771 cells, and Dr. Ravi Amaravadi for Lys05. This 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.).

Publisher Copyright:
© 2019

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology

Accès au document

10.1016/j.celrep.2019.03.037

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DeVorkin, L., Pavey, N., Carleton, G., Comber, A., Ho, C., Lim, J., McNamara, E., Huang, H., Kim, P., Zacharias, L. G., Mizushima, N., Saitoh, T., Akira, S., Beckham, W., Lorzadeh, A., Moksa, M., Cao, Q., Murthy, A., Hirst, M., ... Lum, J. J. (2019). Autophagy Regulation of Metabolism Is Required for CD8 ⁺ T Cell Anti-tumor Immunity Cell Reports, 27(2), 502-513.e5. https://doi.org/10.1016/j.celrep.2019.03.037

DeVorkin, L, Pavey, N, Carleton, G, Comber, A, Ho, C, Lim, J, McNamara, E, Huang, H, Kim, P, Zacharias, LG, Mizushima, N, Saitoh, T, Akira, S, Beckham, W, Lorzadeh, A, Moksa, M, Cao, Q, Murthy, A, Hirst, M, DeBerardinis, RJ & Lum, JJ 2019, ' Autophagy Regulation of Metabolism Is Required for CD8 ⁺ T Cell Anti-tumor Immunity ', Cell Reports, vol. 27, n° 2, pp. 502-513.e5. https://doi.org/10.1016/j.celrep.2019.03.037

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title = " Autophagy Regulation of Metabolism Is Required for CD8 + T Cell Anti-tumor Immunity ",

abstract = " DeVorkin et al. show that loss of autophagy enhances CD8 + T-cell-mediated rejection of tumors. Mechanistically, suppression of autophagy shifts T cells to a glycolytic phenotype and causes a reduction in S-adenosylmethionine. As a consequence, autophagy-deficient T cells transcriptionally reprogram immune response genes to an effector memory state. ",

author = "Lindsay DeVorkin and Nils Pavey and Gillian Carleton and Alexandra Comber and Cally Ho and Junghyun Lim and Erin McNamara and Haochu Huang and Paul Kim and Zacharias, {Lauren G.} and Noboru Mizushima and Tatsuya Saitoh and Shizuo Akira and Wayne Beckham and Alireza Lorzadeh and Michelle Moksa and Qi Cao and Aditya Murthy and Martin Hirst and DeBerardinis, {Ralph J.} and Lum, {Julian J.}",

note = "Funding Information: The authors would like to thank Chris Johnstone and Dr. Magdalena Bazalova-Carter for assistance with radiation of mice to create the bone marrow chimeras, Dr. John Stagg for the e0771 cells, and Dr. Ravi Amaravadi for Lys05. This 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.). Conceptualization, L.D. and J.J.L.; Methodology, L.D. N.P. M.H. A.M. and J.J.L.; Investigation, L.D. N.P. G.C. A.C. C.H. P.K. J.L. E.M, H.H, L.G.Z. N.M. T.S. S.A. W.B. A.L. M.M. and Q.C.; Writing – Original Draft and Revisions, all authors; Visualization, L.D. A.C. and J.J.L. Supervision, L.D, A.M. M.H. and J.J.L. Funding Acquisition, L.D and J.J.L. R.J.D. is member of the Scientific Advisory Board at Agios Pharmaceuticals. A.M. J.L. E.M. and H.H. are employees of Genentech Inc. L.D. and J.J.L. are named inventors on a provisional patent related to the research in this manuscript. Funding Information: The authors would like to thank Chris Johnstone and Dr. Magdalena Bazalova-Carter for assistance with radiation of mice to create the bone marrow chimeras, Dr. John Stagg for the e0771 cells, and Dr. Ravi Amaravadi for Lys05. This 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.). Publisher Copyright: {\textcopyright} 2019",

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AU - Carleton, Gillian

AU - Comber, Alexandra

AU - Ho, Cally

AU - Lim, Junghyun

AU - McNamara, Erin

AU - Huang, Haochu

AU - Kim, Paul

AU - Zacharias, Lauren G.

AU - Mizushima, Noboru

AU - Saitoh, Tatsuya

AU - Akira, Shizuo

AU - Beckham, Wayne

AU - Lorzadeh, Alireza

AU - Moksa, Michelle

AU - Cao, Qi

AU - Murthy, Aditya

AU - Hirst, Martin

AU - DeBerardinis, Ralph J.

AU - Lum, Julian J.

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