CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors.

Détails

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Etat: Public
Version: Author's accepted manuscript
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ID Serval
serval:BIB_B4EB98E7D705
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors.
Périodique
Nature immunology
Auteur(s)
Wang H., Franco F., Tsui Y.C., Xie X., Trefny M.P., Zappasodi R., Mohmood S.R., Fernández-García J., Tsai C.H., Schulze I., Picard F., Meylan E., Silverstein R., Goldberg I., Fendt S.M., Wolchok J.D., Merghoub T., Jandus C., Zippelius A., Ho P.C.
ISSN
1529-2916 (Electronic)
ISSN-L
1529-2908
Statut éditorial
Publié
Date de publication
03/2020
Peer-reviewed
Oui
Volume
21
Numéro
3
Pages
298-308
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Depleting regulatory T cells (T <sub>reg</sub> 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 T <sub>reg</sub> cells is direly needed for cancer immunotherapy. We found that CD36 was selectively upregulated in intrautumoral T <sub>reg</sub> cells as a central metabolic modulator. CD36 fine-tuned mitochondrial fitness via peroxisome proliferator-activated receptor-β signaling, programming T <sub>reg</sub> cells to adapt to a lactic acid-enriched TME. Genetic ablation of Cd36 in T <sub>reg</sub> cells suppressed tumor growth accompanied by a decrease in intratumoral T <sub>reg</sub> 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 T <sub>reg</sub> cells, and the therapeutic potential of targeting this pathway for reprogramming the TME.
Mots-clé
Animals, Apoptosis/immunology, CD36 Antigens/deficiency, CD36 Antigens/genetics, CD36 Antigens/immunology, Cell Line, Tumor, Female, Homeostasis/immunology, Humans, Immunotherapy, Lipid Metabolism/genetics, Lymphocytes, Tumor-Infiltrating/immunology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neoplasms/immunology, Neoplasms/metabolism, Neoplasms/pathology, PPAR-beta/immunology, Signal Transduction/immunology, T-Lymphocytes, Regulatory/immunology, T-Lymphocytes, Regulatory/metabolism, T-Lymphocytes, Regulatory/pathology, Tumor Microenvironment/immunology
Pubmed
Web of science
Création de la notice
20/02/2020 16:32
Dernière modification de la notice
30/04/2021 7:14
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