Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors
Xu S, Chaudhary O, Rodríguez-Morales P, Sun X, Chen D, Zappasodi R, Xu Z, Pinto AFM, Williams A, Schulze I, Farsakoglu Y, Varanasi SK, Low JS, Tang W, Wang H, McDonald B, Tripple V, Downes M, Evans RM, Abumrad NA, Merghoub T, Wolchok JD, Shokhirev MN, Ho PC, Witztum JL, Emu B, Cui G, Kaech SM. Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors. Immunity 2021, 54: 1561-1577.e7. PMID: 34102100, PMCID: PMC9273026, DOI: 10.1016/j.immuni.2021.05.003.Peer-Reviewed Original ResearchConceptsTumor microenvironmentCell dysfunctionLipid peroxidationLipid accumulationOxidized low-density lipoproteinExpression of CD36Low-density lipoproteinCommon metabolic alterationsScavenger receptor CD36Intratumoral CD8Immune dysfunctionEffector TGlutathione peroxidase 4CD8Effector functionsInhibition of p38Metabolic alterationsReceptor CD36Therapeutic avenuesScavenger receptorsDysfunctionWT counterpartsTILsCell functionCD36The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion
Globig A, Zhao S, Roginsky J, Maltez V, Guiza J, Avina-Ochoa N, Heeg M, Araujo Hoffmann F, Chaudhary O, Wang J, Senturk G, Chen D, O’Connor C, Pfaff S, Germain R, Schalper K, Emu B, Kaech S. The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature 2023, 622: 383-392. PMID: 37731001, PMCID: PMC10871066, DOI: 10.1038/s41586-023-06568-6.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCell exhaustionExhausted CD8Sympathetic nervesT cell exhaustionSympathetic stress responsePancreatic cancer modelAnti-tumor functionCheckpoint blockadeCatecholamine levelsTissue innervationCytokine productionChronic antigenMalignant diseaseChronic infectionCD8Immune responseAdrenergic signalingEffector functionsΒ-blockersViral infectionCancer modelExhausted stateCell responsesCell function