{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Riesenberg BP"],"funding":["NIDCR NIH HHS","NIAID NIH HHS","National Cancer Institute","NCI NIH HHS"],"pagination":["4386-4399"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9722626"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["82(23)"],"pubmed_abstract":["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."],"journal":["Cancer research"],"pubmed_title":["Stress-Mediated Attenuation of Translation Undermines T-cell Activity in Cancer."],"pmcid":["PMC9722626"],"funding_grant_id":["T32 5T32AI132164-04","P30 CA138313","T32 AI132164","R01 CA244361","T32 DE01755","T32 DE017551","R01CA244361-01A1","T32 CA 193201","R01CA248359-01","R01 CA248359","T32 CA193201"],"pubmed_authors":["Tennant MD","Hill EG","Andrews AM","Gao P","Hunt EG","Paulos CM","Thaxton JE","Riesenberg BP","Rivera GOR","Leddy LR","Hurst KE","Neskey DM"],"additional_accession":[]},"is_claimable":false,"name":"Stress-Mediated Attenuation of Translation Undermines T-cell Activity in Cancer.","description":"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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-05-29T05:19:23.237Z","creation":"2024-11-09T22:37:48.569Z"},"accession":"S-EPMC9722626","cross_references":{"pubmed":["36126165"],"doi":["10.1158/0008-5472.can-22-1744","10.1158/0008-5472.CAN-22-1744"]}}