@article{866a9f17aaef4cd0a11c47595fa3895f,
title = "CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors",
abstract = "Depleting regulatory T cells (Treg cells) to counteract immunosuppressive features of the tumor microenvironment (TME) is an attractive strategy for cancer treatment; however, autoimmunity due to systemic impairment of their suppressive function limits its therapeutic potential. Elucidating approaches that specifically disrupt intratumoral Treg cells is direly needed for cancer immunotherapy. We found that CD36 was selectively upregulated in intrautumoral Treg cells as a central metabolic modulator. CD36 fine-tuned mitochondrial fitness via peroxisome proliferator-activated receptor-β signaling, programming Treg cells to adapt to a lactic acid-enriched TME. Genetic ablation of Cd36 in Treg cells suppressed tumor growth accompanied by a decrease in intratumoral Treg cells and enhancement of antitumor activity in tumor-infiltrating lymphocytes without disrupting immune homeostasis. Furthermore, CD36 targeting elicited additive antitumor responses with anti-programmed cell death protein 1 therapy. Our findings uncover the unexplored metabolic adaptation that orchestrates the survival and functions of intratumoral Treg cells, and the therapeutic potential of targeting this pathway for reprogramming the TME.",
author = "Haiping Wang and Fabien Franco and Tsui, {Yao Chen} and Xin Xie and Trefny, {Marcel P.} and Roberta Zappasodi and Mohmood, {Syed Raza} and Juan Fern{\'a}ndez-Garc{\'i}a and Tsai, {Chin Hsien} and Isabell Schulze and Florence Picard and Etienne Meylan and Roy Silverstein and Ira Goldberg and Fendt, {Sarah Maria} and Wolchok, {Jedd D.} and Taha Merghoub and Camilla Jandus and Alfred Zippelius and Ho, {Ping Chih}",
note = "Funding Information: We thank L.-F. Lu and W.-L. Lo for critical reading and comments. We also thank Y. Maeda and H. Nishikawa for helpful discussion. P.-C.H. was supported in part by the SNSF (project grants 31003A_163204 and 31003A_182470), the Swiss Cancer Foundation (KFS-3949-08-2016), the Swiss Institute for Experimental Cancer Research (ISREC 26075483), a European Research Council Staring Grant (802773-MitoGuide), the Cancer Research Institute Clinic and Laboratory Integration Program award and the SITC-MRA Young Investigator Award. C.J. is supported by the SNSF (project grants PMPDP3_129022 and PZ00P3_161459). A.Z. is supported by the SNSF (project grant 320030_162575) and Cancer League Switzerland (KFS-3394-02-2014). R.S. and I.G. are supported by NIH funding (P01 HL46403, P01 HL087018 and R01 HL142152 to R.S. and HL45095 and HL073029 to I.G.). E.M. acknowledges funding from the Swiss Cancer Research Foundation (KFS-3681-08-2015-R). S.-M.F. acknowledges funding from an FWO grant and projects, as well as KU Leuven Methusalem co-funding. J.F.-G. is supported by an FWO postdoctoral fellowship. J.D.W and T.M. are supported by NIH funding (P30 CA008748 and R01 CA056821), Swim Across America, the Ludwig Institute for Cancer Research, the Parker Institute for Cancer Immunotherapy and the Breast Cancer Research Foundation. R.Z. is supported by the Parker Institute for Cancer Immunotherapy Bridge Scholar Award. We also appreciate the support provided by the Electron Microscopy Facility at the University of Lausanne and the Biomedical Sequencing Facility at the Research Center for Molecular Medicine of the Austrian Academy of Sciences. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = mar,
day = "1",
doi = "10.1038/s41590-019-0589-5",
language = "English (US)",
volume = "21",
pages = "298--308",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "3",
}