Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8<sup>+</sup> T cells in tumors.

Détails

ID Serval
serval:BIB_7490E53D6718
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8<sup>+</sup> T cells in tumors.
Périodique
Immunity
Auteur(s)
Xu S., Chaudhary O., Rodríguez-Morales P., Sun X., Chen D., Zappasodi R., Xu Z., Pinto AFM, Williams A., Schulze I., Farsakoglu Y., Varanasi S.K., Low J.S., Tang W., Wang H., McDonald B., Tripple V., Downes M., Evans R.M., Abumrad N.A., Merghoub T., Wolchok J.D., Shokhirev M.N., Ho P.C., Witztum J.L., Emu B., Cui G., Kaech S.M.
ISSN
1097-4180 (Electronic)
ISSN-L
1074-7613
Statut éditorial
Publié
Date de publication
13/07/2021
Peer-reviewed
Oui
Volume
54
Numéro
7
Pages
1561-1577.e7
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
A common metabolic alteration in the tumor microenvironment (TME) is lipid accumulation, a feature associated with immune dysfunction. Here, we examined how CD8 <sup>+</sup> tumor infiltrating lymphocytes (TILs) respond to lipids within the TME. We found elevated concentrations of several classes of lipids in the TME and accumulation of these in CD8 <sup>+</sup> TILs. Lipid accumulation was associated with increased expression of CD36, a scavenger receptor for oxidized lipids, on CD8 <sup>+</sup> TILs, which also correlated with progressive T cell dysfunction. Cd36 <sup>-/-</sup> T cells retained effector functions in the TME, as compared to WT counterparts. Mechanistically, CD36 promoted uptake of oxidized low-density lipoproteins (OxLDL) into T cells, and this induced lipid peroxidation and downstream activation of p38 kinase. Inhibition of p38 restored effector T cell functions in vitro, and resolution of lipid peroxidation by overexpression of glutathione peroxidase 4 restored functionalities in CD8 <sup>+</sup> TILs in vivo. Thus, an oxidized lipid-CD36 axis promotes intratumoral CD8 <sup>+</sup> T cell dysfunction and serves as a therapeutic avenue for immunotherapies.
Mots-clé
CD36, CD8(+) T cells, lipid peroxidation, oxidized lipids, tumor microenvironment, CD8(+) T cells
Pubmed
Web of science
Création de la notice
15/06/2021 15:46
Dernière modification de la notice
31/07/2021 6:34
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