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000169133 041__ $$aEnglish
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000169133 1001_ $$aXu, Shihao$$b0
000169133 245__ $$aUptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors.
000169133 260__ $$aNew York, NY$$bElsevier$$c2021
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000169133 500__ $$a2021 Jul 13;54(7):1561-1577.e7
000169133 520__ $$aA common metabolic alteration in the tumor microenvironment (TME) is lipid accumulation, a feature associated with immune dysfunction. Here, we examined how CD8+ tumor infiltrating lymphocytes (TILs) respond to lipids within the TME. We found elevated concentrations of several classes of lipids in the TME and accumulation of these in CD8+ TILs. Lipid accumulation was associated with increased expression of CD36, a scavenger receptor for oxidized lipids, on CD8+ TILs, which also correlated with progressive T cell dysfunction. Cd36-/- T cells retained effector functions in the TME, as compared to WT counterparts. Mechanistically, CD36 promoted uptake of oxidized low-density lipoproteins (OxLDL) into T cells, and this induced lipid peroxidation and downstream activation of p38 kinase. Inhibition of p38 restored effector T cell functions in vitro, and resolution of lipid peroxidation by overexpression of glutathione peroxidase 4 restored functionalities in CD8+ TILs in vivo. Thus, an oxidized lipid-CD36 axis promotes intratumoral CD8+ T cell dysfunction and serves as a therapeutic avenue for immunotherapies.
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000169133 650_7 $$2Other$$aCD36
000169133 650_7 $$2Other$$aCD8(+) T cells
000169133 650_7 $$2Other$$alipid peroxidation
000169133 650_7 $$2Other$$aoxidized lipids
000169133 650_7 $$2Other$$atumor microenvironment
000169133 7001_ $$aChaudhary, Omkar$$b1
000169133 7001_ $$aRodríguez-Morales, Patricia$$b2
000169133 7001_ $$aSun, Xiaoli$$b3
000169133 7001_ $$aChen, Dan$$b4
000169133 7001_ $$aZappasodi, Roberta$$b5
000169133 7001_ $$aXu, Ziyan$$b6
000169133 7001_ $$aPinto, Antonio F M$$b7
000169133 7001_ $$aWilliams, April$$b8
000169133 7001_ $$aSchulze, Isabell$$b9
000169133 7001_ $$aFarsakoglu, Yagmur$$b10
000169133 7001_ $$aVaranasi, Siva Karthik$$b11
000169133 7001_ $$aLow, Jun Siong$$b12
000169133 7001_ $$aTang, Wenxi$$b13
000169133 7001_ $$aWang, Haiping$$b14
000169133 7001_ $$aMcDonald, Bryan$$b15
000169133 7001_ $$aTripple, Victoria$$b16
000169133 7001_ $$aDownes, Michael$$b17
000169133 7001_ $$aEvans, Ronald M$$b18
000169133 7001_ $$aAbumrad, Nada A$$b19
000169133 7001_ $$aMerghoub, Taha$$b20
000169133 7001_ $$aWolchok, Jedd D$$b21
000169133 7001_ $$aShokhirev, Maxim N$$b22
000169133 7001_ $$aHo, Ping-Chih$$b23
000169133 7001_ $$aWitztum, Joseph L$$b24
000169133 7001_ $$aEmu, Brinda$$b25
000169133 7001_ $$0P:(DE-He78)0b7ce76033a6756b91f5bfb12602e20b$$aCui, Guoliang$$b26$$udkfz
000169133 7001_ $$aKaech, Susan M$$b27
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