{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pichler AC"],"funding":["Intramural NIH HHS"],"pagination":["1631-1648.e10"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10649891"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["56(7)"],"pubmed_abstract":["CD137 (4-1BB)-activating receptor represents a promising cancer immunotherapeutic target. Yet, the cellular program driven by CD137 and its role in cancer immune surveillance remain unresolved. Using T cell-specific deletion and agonist antibodies, we found that CD137 modulates tumor infiltration of CD8<sup>+</sup>-exhausted T (Tex) cells expressing PD1, Lag-3, and Tim-3 inhibitory receptors. T cell-intrinsic, TCR-independent CD137 signaling stimulated the proliferation and the terminal differentiation of Tex precursor cells through a mechanism involving the RelA and cRel canonical NF-κB subunits and Tox-dependent chromatin remodeling. While Tex cell accumulation induced by prophylactic CD137 agonists favored tumor growth, anti-PD1 efficacy was improved with subsequent CD137 stimulation in"],"journal":["Immunity"],"pubmed_title":["TCR-independent CD137 (4-1BB) signaling promotes CD8&lt;sup&gt;+&lt;/sup&gt;-exhausted T cell proliferation and terminal differentiation."],"pmcid":["PMC10649891"],"funding_grant_id":["ZIA AI001240"],"pubmed_authors":["Lucca LE","Joffre O","Salomon BL","Blanquart E","Lemaitre L","Tosolini M","Ekren R","Guillerey C","Voisin A","Carrie N","Golec DP","Axisa PP","Watts TH","Cannons JL","Grinberg-Bleyer Y","do Souto L","Pichler AC","Schwartzberg PL","Avet-Loiseau H","Cuisinier M","Joubert MV","Ghazali S","Mazzotti C","Maheo S","Feliu V","Martinet L"],"additional_accession":[]},"is_claimable":false,"name":"TCR-independent CD137 (4-1BB) signaling promotes CD8&lt;sup&gt;+&lt;/sup&gt;-exhausted T cell proliferation and terminal differentiation.","description":"CD137 (4-1BB)-activating receptor represents a promising cancer immunotherapeutic target. Yet, the cellular program driven by CD137 and its role in cancer immune surveillance remain unresolved. Using T cell-specific deletion and agonist antibodies, we found that CD137 modulates tumor infiltration of CD8<sup>+</sup>-exhausted T (Tex) cells expressing PD1, Lag-3, and Tim-3 inhibitory receptors. T cell-intrinsic, TCR-independent CD137 signaling stimulated the proliferation and the terminal differentiation of Tex precursor cells through a mechanism involving the RelA and cRel canonical NF-κB subunits and Tox-dependent chromatin remodeling. While Tex cell accumulation induced by prophylactic CD137 agonists favored tumor growth, anti-PD1 efficacy was improved with subsequent CD137 stimulation in","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jul","modification":"2026-05-29T10:23:41.902Z","creation":"2025-04-06T01:19:09.528Z"},"accession":"S-EPMC10649891","cross_references":{"pubmed":["37392737"],"doi":["10.1016/j.immuni.2023.06.007"]}}