biostudies-literatureRiesenberg BPNIDCR NIH HHSNIAID NIH HHSNational Cancer InstituteNCI NIH HHS4386-4399https://www.ebi.ac.uk/biostudies/studies/S-EPMC9722626biostudies-literatureUnknown82(23)Protein synthesis supports robust immune responses. Nutrient competition and global cell stressors in the tumor microenvironment (TME) may impact protein translation in T cells and antitumor immunity. Using human and mouse tumors, we demonstrated here that protein translation in T cells is repressed in solid tumors. Reduced glucose availability to T cells in the TME led to activation of the unfolded protein response (UPR) element eIF2α (eukaryotic translation initiation factor 2 alpha). Genetic mouse models revealed that translation attenuation mediated by activated p-eIF2α undermines the ability of T cells to suppress tumor growth. Reprograming T-cell metabolism was able to alleviate p-eIF2α accumulation and translational attenuation in the TME, allowing for sustained protein translation.Cancer researchStress-Mediated Attenuation of Translation Undermines T-cell Activity in Cancer.PMC9722626T32 5T32AI132164-04P30 CA138313T32 AI132164R01 CA244361T32 DE01755T32 DE017551R01CA244361-01A1T32 CA 193201R01CA248359-01R01 CA248359T32 CA193201Tennant MDHill EGAndrews AMGao PHunt EGPaulos CMThaxton JERiesenberg BPRivera GORLeddy LRHurst KENeskey DMfalseStress-Mediated Attenuation of Translation Undermines T-cell Activity in Cancer.Protein synthesis supports robust immune responses. Nutrient competition and global cell stressors in the tumor microenvironment (TME) may impact protein translation in T cells and antitumor immunity. Using human and mouse tumors, we demonstrated here that protein translation in T cells is repressed in solid tumors. Reduced glucose availability to T cells in the TME led to activation of the unfolded protein response (UPR) element eIF2α (eukaryotic translation initiation factor 2 alpha). Genetic mouse models revealed that translation attenuation mediated by activated p-eIF2α undermines the ability of T cells to suppress tumor growth. Reprograming T-cell metabolism was able to alleviate p-eIF2α accumulation and translational attenuation in the TME, allowing for sustained protein translation.2022-01-01T00:00:00Z2022 Dec2026-05-29T05:19:23.237Z2024-11-09T22:37:48.569ZS-EPMC97226263612616510.1158/0008-5472.can-22-174410.1158/0008-5472.CAN-22-1744