{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chen J"],"funding":["National Natural Science Foundation of China"],"pagination":["1290-1301"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9622748"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(11)"],"pubmed_abstract":["PD-L1<sup>+</sup> tumor-derived extracellular vesicles (TEVs) cause systemic immunosuppression and possibly resistance to anti-PD-L1 antibody (αPD-L1) blockade. However, whether and how PD-L1<sup>+</sup> TEVs mediate αPD-L1 therapy resistance is unknown. Here, we show that PD-L1<sup>+</sup> TEVs substantially decoy αPD-L1 and that TEV-bound αPD-L1 is more rapidly cleared by macrophages, causing insufficient blockade of tumor PD-L1 and subsequent αPD-L1 therapy resistance. Inhibition of endogenous production of TEVs by Rab27a or Coro1a knockout reverses αPD-L1 therapy resistance. Either an increased αPD-L1 dose or macrophage depletion mediated by the clinical drug pexidartinib abolishes αPD-L1 therapy resistance. Moreover, in the treatment cycle with the same total treatment dose of αPD-L1,"],"journal":["Cellular & molecular immunology"],"pubmed_title":["Tumor extracellular vesicles mediate anti-PD-L1 therapy resistance by decoying anti-PD-L1."],"pmcid":["PMC9622748"],"funding_grant_id":["31970845","81901571","81971871","31870876"],"pubmed_authors":["Zhang G","Yang J","Chen J","Lu X","Zhang J","Wang J","Wang P","Wang S","Huang X","Cai Z","Wang W","Guo D","Zhang C"],"additional_accession":[]},"is_claimable":false,"name":"Tumor extracellular vesicles mediate anti-PD-L1 therapy resistance by decoying anti-PD-L1.","description":"PD-L1<sup>+</sup> tumor-derived extracellular vesicles (TEVs) cause systemic immunosuppression and possibly resistance to anti-PD-L1 antibody (αPD-L1) blockade. However, whether and how PD-L1<sup>+</sup> TEVs mediate αPD-L1 therapy resistance is unknown. Here, we show that PD-L1<sup>+</sup> TEVs substantially decoy αPD-L1 and that TEV-bound αPD-L1 is more rapidly cleared by macrophages, causing insufficient blockade of tumor PD-L1 and subsequent αPD-L1 therapy resistance. Inhibition of endogenous production of TEVs by Rab27a or Coro1a knockout reverses αPD-L1 therapy resistance. Either an increased αPD-L1 dose or macrophage depletion mediated by the clinical drug pexidartinib abolishes αPD-L1 therapy resistance. Moreover, in the treatment cycle with the same total treatment dose of αPD-L1,","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2025-04-04T08:45:12.719Z","creation":"2025-04-04T08:45:12.719Z"},"accession":"S-EPMC9622748","cross_references":{"pubmed":["36220994"],"doi":["10.1038/s41423-022-00926-6"]}}