Journal article
CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors.
- Wang H Department of Oncology, University of Lausanne, Lausanne, Switzerland.
- Franco F Department of Oncology, University of Lausanne, Lausanne, Switzerland.
- Tsui YC Department of Oncology, University of Lausanne, Lausanne, Switzerland.
- Xie X Center for Genomics and Systems Biology, NYU Abu Dhabi, Abu Dhabi, United Arab Emirates.
- Trefny MP Department of Biomedicine, Laboratory of Cancer Immunology, University Hospital and University of Basel, Basel, Switzerland.
- Zappasodi R Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Mohmood SR Center for Genomics and Systems Biology, NYU Abu Dhabi, Abu Dhabi, United Arab Emirates.
- Fernández-García J Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium.
- Tsai CH Department of Oncology, University of Lausanne, Lausanne, Switzerland.
- Schulze I Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Picard F Department of Oncology, University of Lausanne, Lausanne, Switzerland.
- Meylan E Swiss Institute for Experimental Cancer Research, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
- Silverstein R Department of Medicine, Medical College of Wisconsin, Wauwatosa, WI, USA.
- Goldberg I Department of Medicine, NYU Langone Health, New York, NY, USA.
- Fendt SM Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium.
- Wolchok JD Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Merghoub T Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Jandus C Department of Oncology, University of Lausanne, Lausanne, Switzerland.
- Zippelius A Department of Biomedicine, Laboratory of Cancer Immunology, University Hospital and University of Basel, Basel, Switzerland.
- Ho PC Department of Oncology, University of Lausanne, Lausanne, Switzerland. ping-chih.ho@unil.ch.
- 2020-02-19
Published in:
- Nature immunology. - 2020
Animals
Apoptosis
CD36 Antigens
Cell Line, Tumor
Female
Homeostasis
Humans
Immunotherapy
Lipid Metabolism
Lymphocytes, Tumor-Infiltrating
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasms
PPAR-beta
Signal Transduction
T-Lymphocytes, Regulatory
Tumor Microenvironment
English
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.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1038/s41590-019-0589-5
- PMID 32066953
- Persistent URL
- https://sonar.ch/global/documents/247082
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