| First Author | Xu S | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 7 | Pages | 1561-1577.e7 |
| PubMed ID | 34102100 | Mgi Jnum | J:360367 |
| Mgi Id | MGI:6740307 | Doi | 10.1016/j.immuni.2021.05.003 |
| Citation | Xu S, et al. (2021) Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8(+) T cells in tumors. Immunity 54(7):1561-1577.e7 |
| abstractText | A common metabolic alteration in the tumor microenvironment (TME) is lipid accumulation, a feature associated with immune dysfunction. Here, we examined how CD8(+) 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(+) TILs. Lipid accumulation was associated with increased expression of CD36, a scavenger receptor for oxidized lipids, on CD8(+) TILs, which also correlated with progressive T cell dysfunction. Cd36(-/-) 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(+) TILs in vivo. Thus, an oxidized lipid-CD36 axis promotes intratumoral CD8(+) T cell dysfunction and serves as a therapeutic avenue for immunotherapies. |
