Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity

Alison E. Ringel; Jefte M. Drijvers; Gregory J. Baker; Alessia Catozzi; Juan C. García-Cañaveras; Brandon M. Gassaway; Brian C. Miller; Vikram R. Juneja; Thao H. Nguyen; Shakchhi Joshi; Cong Hui Yao; Haejin Yoon; Peter T. Sage; Martin W. LaFleur; Justin D. Trombley; Connor A. Jacobson; Zoltan Maliga; Steven P. Gygi; Peter K. Sorger; Joshua D. Rabinowitz; Arlene H. Sharpe; Marcia C. Haigis

doi:10.1016/j.cell.2020.11.009

Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity

Alison E. Ringel, Jefte M. Drijvers, Gregory J. Baker, Alessia Catozzi, Juan C. García-Cañaveras, Brandon M. Gassaway, Brian C. Miller, Vikram R. Juneja, Thao H. Nguyen, Shakchhi Joshi, Cong Hui Yao, Haejin Yoon, Peter T. Sage, Martin W. LaFleur, Justin D. Trombley, Connor A. Jacobson, Zoltan Maliga, Steven P. Gygi, Peter K. Sorger, Joshua D. RabinowitzArlene H. Sharpe, Marcia C. Haigis

Research output: Contribution to journal › Article › peer-review

284 Scopus citations

Abstract

High-fat diet compromises anti-tumor immunity by interfering with metabolism in the tumor microenvironment.

Original language	English (US)
Pages (from-to)	1848-1866.e26
Journal	Cell
Volume	183
Issue number	7
DOIs	https://doi.org/10.1016/j.cell.2020.11.009
State	Published - Dec 23 2020

All Science Journal Classification (ASJC) codes

Biochemistry, Genetics and Molecular Biology(all)

Keywords

CD8+ T cells
anti-tumor immunity
colorectal cancer
fat oxidation
metabolism
obesity
tumor microenvironment

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10.1016/j.cell.2020.11.009

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Ringel, A. E., Drijvers, J. M., Baker, G. J., Catozzi, A., García-Cañaveras, J. C., Gassaway, B. M., Miller, B. C., Juneja, V. R., Nguyen, T. H., Joshi, S., Yao, C. H., Yoon, H., Sage, P. T., LaFleur, M. W., Trombley, J. D., Jacobson, C. A., Maliga, Z., Gygi, S. P., Sorger, P. K., ... Haigis, M. C. (2020). Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity. Cell, 183(7), 1848-1866.e26. https://doi.org/10.1016/j.cell.2020.11.009

@article{f59881aa54c940a18cd8ba5b1ec2c8aa,

title = "Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity",

abstract = "High-fat diet compromises anti-tumor immunity by interfering with metabolism in the tumor microenvironment.",

keywords = "CD8+ T cells, anti-tumor immunity, colorectal cancer, fat oxidation, metabolism, obesity, tumor microenvironment",

author = "Ringel, {Alison E.} and Drijvers, {Jefte M.} and Baker, {Gregory J.} and Alessia Catozzi and Garc{\'i}a-Ca{\~n}averas, {Juan C.} and Gassaway, {Brandon M.} and Miller, {Brian C.} and Juneja, {Vikram R.} and Nguyen, {Thao H.} and Shakchhi Joshi and Yao, {Cong Hui} and Haejin Yoon and Sage, {Peter T.} and LaFleur, {Martin W.} and Trombley, {Justin D.} and Jacobson, {Connor A.} and Zoltan Maliga and Gygi, {Steven P.} and Sorger, {Peter K.} and Rabinowitz, {Joshua D.} and Sharpe, {Arlene H.} and Haigis, {Marcia C.}",

note = "Funding Information: We are grateful for resources provided by the “MicRoN core at Harvard Medical School” and “HMS Immunology Flow Cytometry Core Facility.” This study was supported by grants from the Ludwig Center at Harvard Medical School (United States; to M.C.H., A.H.S., and P.K.S), NCI (National Cancer Institute, United States; U54-CA225088 to M.C.H., A.H.S., and P.K.S. and R01CA213062 to M.C.H.), the Evergrande Center for Immunologic Disease (to A.H.S.), the Glenn Foundation for Medical Research (United States; to M.C.H.), and NIH ( National Institute of Diabetes and Digestive and Kidney Diseases, United States; R01DK103295 to M.C.H. and P01 AI56299 to A.H.S). A.E.R was supported by postdoctoral fellowships from the American Cancer Society (United States; 130373-PF-17-132-01-CCG ) and Cell Biology Education and Fellowship Fund (United States; Harvard Medical School) . J.M.D. was supported by a predoctoral F31 NIH fellowship (National Institutes of Health, United States; 5F31CA224601 ). M.W.L. was supported by a predoctoral T32 NIH fellowship (National Institutes of Health, United States; T32CA207021 ). The VUMC Hormone Assay & Analytical Services and Lipid Cores are supported by NIH (National Institute of Diabetes and Digestive and Kidney Diseases, United States; DK059637 to MMPC and DK020593 to DRTC). Funding Information: We are grateful for resources provided by the ?MicRoN core at Harvard Medical School? and ?HMS Immunology Flow Cytometry Core Facility.? This study was supported by grants from the Ludwig Center at Harvard Medical School (United States; to M.C.H. A.H.S. and P.K.S), NCI (National Cancer Institute, United States; U54-CA225088 to M.C.H. A.H.S. and P.K.S. and R01CA213062 to M.C.H.), the Evergrande Center for Immunologic Disease (to A.H.S.), the Glenn Foundation for Medical Research (United States; to M.C.H.), and NIH (National Institute of Diabetes and Digestive and Kidney Diseases, United States; R01DK103295 to M.C.H. and P01 AI56299 to A.H.S). A.E.R was supported by postdoctoral fellowships from the American Cancer Society (United States; 130373-PF-17-132-01-CCG) and Cell Biology Education and Fellowship Fund (United States; Harvard Medical School). J.M.D. was supported by a predoctoral F31 NIH fellowship (National Institutes of Health, United States; 5F31CA224601). M.W.L. was supported by a predoctoral T32 NIH fellowship (National Institutes of Health, United States; T32CA207021). The VUMC Hormone Assay & Analytical Services and Lipid Cores are supported by NIH (National Institute of Diabetes and Digestive and Kidney Diseases, United States; DK059637 to MMPC and DK020593 to DRTC). Conceptualization, A.E.R. J.M.D. M.C.H. and A.H.S.; Software, G.J.B. A.E.R. and B.C.M.; Formal Analysis, A.E.R. J.M.D. and G.J.B.; Investigation, A.E.R. J.M.D. G.J.B. A.C. J.C.G.-C. B.M.G. B.C.M. V.R.J. T.H.N. S.J. C.-H.Y. H.Y. P.T.S. M.W.L. J.D.T. C.A.J. and Z.M.; Writing ? Original Draft, A.E.R. and J.M.D.; Writing ? Review & Editing, A.E.R. J.M.D. M.C.H. and A.H.S.; Visualization, A.E.R. and J.M.D.; Supervision, M.C.H. A.H.S. S.P.G. P.K.S. and J.D.R.; Funding Acquisition, M.C.H. and A.H.S. A.H.S. has patents/pending royalties on intellectual property on the PD-1 pathway from Roche and Novartis. A.H.S. is on advisory boards for Surface Oncology, Elstar, SQZ Biotechnologies, Selecta, Elpiscience, and Monopteros and has research funding from Novartis, Roche, Ipsen, Quark, and Merck. M.C.H. has patents pending on the PHD3 pathway, is on the scientific advisory board for Pori Therapeutics, and has research funding from Roche. J.M.D. has consulted for ElevateBio and Third Rock Ventures. The remaining authors declare no competing interests. Funding Information: A.H.S. has patents/pending royalties on intellectual property on the PD-1 pathway from Roche and Novartis. A.H.S. is on advisory boards for Surface Oncology, Elstar, SQZ Biotechnologies, Selecta, Elpiscience, and Monopteros and has research funding from Novartis, Roche, Ipsen, Quark, and Merck. M.C.H. has patents pending on the PHD3 pathway, is on the scientific advisory board for Pori Therapeutics, and has research funding from Roche. J.M.D. has consulted for ElevateBio and Third Rock Ventures. The remaining authors declare no competing interests. Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = dec,

day = "23",

doi = "10.1016/j.cell.2020.11.009",

language = "English (US)",

volume = "183",

pages = "1848--1866.e26",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "7",

}

Ringel, AE, Drijvers, JM, Baker, GJ, Catozzi, A, García-Cañaveras, JC, Gassaway, BM, Miller, BC, Juneja, VR, Nguyen, TH, Joshi, S, Yao, CH, Yoon, H, Sage, PT, LaFleur, MW, Trombley, JD, Jacobson, CA, Maliga, Z, Gygi, SP, Sorger, PK, Rabinowitz, JD, Sharpe, AH & Haigis, MC 2020, 'Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity', Cell, vol. 183, no. 7, pp. 1848-1866.e26. https://doi.org/10.1016/j.cell.2020.11.009

TY - JOUR

T1 - Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity

AU - Ringel, Alison E.

AU - Drijvers, Jefte M.

AU - Baker, Gregory J.

AU - Catozzi, Alessia

AU - García-Cañaveras, Juan C.

AU - Gassaway, Brandon M.

AU - Miller, Brian C.

AU - Juneja, Vikram R.

AU - Nguyen, Thao H.

AU - Joshi, Shakchhi

AU - Yao, Cong Hui

AU - Yoon, Haejin

AU - Sage, Peter T.

AU - LaFleur, Martin W.

AU - Trombley, Justin D.

AU - Jacobson, Connor A.

AU - Maliga, Zoltan

AU - Gygi, Steven P.

AU - Sorger, Peter K.

AU - Rabinowitz, Joshua D.

AU - Sharpe, Arlene H.

AU - Haigis, Marcia C.

N1 - Funding Information: We are grateful for resources provided by the “MicRoN core at Harvard Medical School” and “HMS Immunology Flow Cytometry Core Facility.” This study was supported by grants from the Ludwig Center at Harvard Medical School (United States; to M.C.H., A.H.S., and P.K.S), NCI (National Cancer Institute, United States; U54-CA225088 to M.C.H., A.H.S., and P.K.S. and R01CA213062 to M.C.H.), the Evergrande Center for Immunologic Disease (to A.H.S.), the Glenn Foundation for Medical Research (United States; to M.C.H.), and NIH ( National Institute of Diabetes and Digestive and Kidney Diseases, United States; R01DK103295 to M.C.H. and P01 AI56299 to A.H.S). A.E.R was supported by postdoctoral fellowships from the American Cancer Society (United States; 130373-PF-17-132-01-CCG ) and Cell Biology Education and Fellowship Fund (United States; Harvard Medical School) . J.M.D. was supported by a predoctoral F31 NIH fellowship (National Institutes of Health, United States; 5F31CA224601 ). M.W.L. was supported by a predoctoral T32 NIH fellowship (National Institutes of Health, United States; T32CA207021 ). The VUMC Hormone Assay & Analytical Services and Lipid Cores are supported by NIH (National Institute of Diabetes and Digestive and Kidney Diseases, United States; DK059637 to MMPC and DK020593 to DRTC). Funding Information: We are grateful for resources provided by the ?MicRoN core at Harvard Medical School? and ?HMS Immunology Flow Cytometry Core Facility.? This study was supported by grants from the Ludwig Center at Harvard Medical School (United States; to M.C.H. A.H.S. and P.K.S), NCI (National Cancer Institute, United States; U54-CA225088 to M.C.H. A.H.S. and P.K.S. and R01CA213062 to M.C.H.), the Evergrande Center for Immunologic Disease (to A.H.S.), the Glenn Foundation for Medical Research (United States; to M.C.H.), and NIH (National Institute of Diabetes and Digestive and Kidney Diseases, United States; R01DK103295 to M.C.H. and P01 AI56299 to A.H.S). A.E.R was supported by postdoctoral fellowships from the American Cancer Society (United States; 130373-PF-17-132-01-CCG) and Cell Biology Education and Fellowship Fund (United States; Harvard Medical School). J.M.D. was supported by a predoctoral F31 NIH fellowship (National Institutes of Health, United States; 5F31CA224601). M.W.L. was supported by a predoctoral T32 NIH fellowship (National Institutes of Health, United States; T32CA207021). The VUMC Hormone Assay & Analytical Services and Lipid Cores are supported by NIH (National Institute of Diabetes and Digestive and Kidney Diseases, United States; DK059637 to MMPC and DK020593 to DRTC). Conceptualization, A.E.R. J.M.D. M.C.H. and A.H.S.; Software, G.J.B. A.E.R. and B.C.M.; Formal Analysis, A.E.R. J.M.D. and G.J.B.; Investigation, A.E.R. J.M.D. G.J.B. A.C. J.C.G.-C. B.M.G. B.C.M. V.R.J. T.H.N. S.J. C.-H.Y. H.Y. P.T.S. M.W.L. J.D.T. C.A.J. and Z.M.; Writing ? Original Draft, A.E.R. and J.M.D.; Writing ? Review & Editing, A.E.R. J.M.D. M.C.H. and A.H.S.; Visualization, A.E.R. and J.M.D.; Supervision, M.C.H. A.H.S. S.P.G. P.K.S. and J.D.R.; Funding Acquisition, M.C.H. and A.H.S. A.H.S. has patents/pending royalties on intellectual property on the PD-1 pathway from Roche and Novartis. A.H.S. is on advisory boards for Surface Oncology, Elstar, SQZ Biotechnologies, Selecta, Elpiscience, and Monopteros and has research funding from Novartis, Roche, Ipsen, Quark, and Merck. M.C.H. has patents pending on the PHD3 pathway, is on the scientific advisory board for Pori Therapeutics, and has research funding from Roche. J.M.D. has consulted for ElevateBio and Third Rock Ventures. The remaining authors declare no competing interests. Funding Information: A.H.S. has patents/pending royalties on intellectual property on the PD-1 pathway from Roche and Novartis. A.H.S. is on advisory boards for Surface Oncology, Elstar, SQZ Biotechnologies, Selecta, Elpiscience, and Monopteros and has research funding from Novartis, Roche, Ipsen, Quark, and Merck. M.C.H. has patents pending on the PHD3 pathway, is on the scientific advisory board for Pori Therapeutics, and has research funding from Roche. J.M.D. has consulted for ElevateBio and Third Rock Ventures. The remaining authors declare no competing interests. Publisher Copyright: © 2020

PY - 2020/12/23

Y1 - 2020/12/23

N2 - High-fat diet compromises anti-tumor immunity by interfering with metabolism in the tumor microenvironment.

AB - High-fat diet compromises anti-tumor immunity by interfering with metabolism in the tumor microenvironment.

KW - CD8+ T cells

KW - anti-tumor immunity

KW - colorectal cancer

KW - fat oxidation

KW - metabolism

KW - obesity

KW - tumor microenvironment

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AN - SCOPUS:85097881150

SN - 0092-8674

VL - 183

SP - 1848-1866.e26

JO - Cell

JF - Cell

IS - 7

ER -

Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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