biostudies-literatureHurst KEHHS | National Institutes of HealthAmerican Cancer SocietyNCI NIH HHSNIH HHSNIGMS NIH HHS587-595https://www.ebi.ac.uk/biostudies/studies/S-EPMC11809263biostudies-literatureUnknown8(5)The requisites for protein translation in T cells are poorly understood and how translation shapes the antitumor efficacy of T cells is unknown. Here we demonstrated that IL15-conditioned T cells were primed by the metabolic energy sensor AMP-activated protein kinase to undergo diminished translation relative to effector T cells. However, we showed that IL15-conditioned T cells exhibited a remarkable capacity to enhance their protein translation in tumors, which effector T cells were unable to duplicate. Studying the modulation of translation for applications in cancer immunotherapy revealed that direct ex vivo pharmacologic inhibition of translation elongation primed robust T-cell antitumor immunity. Our work elucidates that altering protein translation in CD8+ T cells cCancer immunology researchRemodeling Translation Primes CD8+ T-cell Antitumor Immunity.PMC11809263S10 OD010731K12 CA157688IRG-16-185-17IRG-97-219-14P20 GM103542S10 OD025126Chung DLawrence KARobino RAThaxton JEHurst KEBall LEfalseRemodeling Translation Primes CD8+ T-cell Antitumor Immunity.The requisites for protein translation in T cells are poorly understood and how translation shapes the antitumor efficacy of T cells is unknown. Here we demonstrated that IL15-conditioned T cells were primed by the metabolic energy sensor AMP-activated protein kinase to undergo diminished translation relative to effector T cells. However, we showed that IL15-conditioned T cells exhibited a remarkable capacity to enhance their protein translation in tumors, which effector T cells were unable to duplicate. Studying the modulation of translation for applications in cancer immunotherapy revealed that direct ex vivo pharmacologic inhibition of translation elongation primed robust T-cell antitumor immunity. Our work elucidates that altering protein translation in CD8+ T cells c2020-01-01T00:00:00Z2020 May2025-04-04T11:58:05.519Z2025-04-04T11:58:05.519ZS-EPMC118092633207580210.1158/2326-6066.CIR-19-051610.1158/2326-6066.cir-19-0516