{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liu S"],"funding":["Natural Science Foundation of Beijing Municipality","National Natural Science Foundation of China","Beijing Natural Science Foundation"],"pagination":["104075"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12907902"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["91"],"pubmed_abstract":["Inhibiting the PD1/PD-L1 interaction is crucial for developing novel cancer immunotherapies, particularly to reduce systemic toxicity and enhance patient response rates. In this study, we designed and synthesized Photodegradation-Targeting Chimeras (PDTACs) by conjugating a clinically approved photosensitizer, verteporfin, to a PD-L1-targeted peptide. Our optimized chimera, PPA-VPF, demonstrates a dual mechanism of action in cancer immunotherapy, resulting from singlet oxygen generated under light irradiation. The proximity-generated singlet oxygen effectively degrades PD-L1 in cancer cells through immediate protein breakdown and resulted in subsequent lysosomal-dependent degradation hours after irradiation. Additionally, the non-proximity-generated singlet oxygen induces immunogenic cell death (ICD) through cytotoxic effects. In mouse models with immune cold tumors, PPA-VPF elicited robust adaptive antitumor immunity and effectively inhibited the growth of both primary and distant tumors. This PD-L1-targeted PDTAC achieved immune checkpoint blockade and ICD induction in a single therapeutic mode using one molecular species, presenting a novel strategy for combinational immunotherapy, particularly in immune cold tumors."],"journal":["Redox biology"],"pubmed_title":["PD-L1-targeted photodynamic therapy orchestrates checkpoint blockade and immunogenic cell death for synergistic cancer immunotherapy."],"pmcid":["PMC12907902"],"funding_grant_id":["82203788","JQ22021","22177008","22377005"],"pubmed_authors":["Yang Z","Li Z","Wang B","Huan S","Wei X","Liu S","Liu G"],"additional_accession":[]},"is_claimable":false,"name":"PD-L1-targeted photodynamic therapy orchestrates checkpoint blockade and immunogenic cell death for synergistic cancer immunotherapy.","description":"Inhibiting the PD1/PD-L1 interaction is crucial for developing novel cancer immunotherapies, particularly to reduce systemic toxicity and enhance patient response rates. In this study, we designed and synthesized Photodegradation-Targeting Chimeras (PDTACs) by conjugating a clinically approved photosensitizer, verteporfin, to a PD-L1-targeted peptide. Our optimized chimera, PPA-VPF, demonstrates a dual mechanism of action in cancer immunotherapy, resulting from singlet oxygen generated under light irradiation. The proximity-generated singlet oxygen effectively degrades PD-L1 in cancer cells through immediate protein breakdown and resulted in subsequent lysosomal-dependent degradation hours after irradiation. Additionally, the non-proximity-generated singlet oxygen induces immunogenic cell death (ICD) through cytotoxic effects. In mouse models with immune cold tumors, PPA-VPF elicited robust adaptive antitumor immunity and effectively inhibited the growth of both primary and distant tumors. This PD-L1-targeted PDTAC achieved immune checkpoint blockade and ICD induction in a single therapeutic mode using one molecular species, presenting a novel strategy for combinational immunotherapy, particularly in immune cold tumors.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-09T10:16:01.703Z","creation":"2026-07-09T10:14:01.083Z"},"accession":"S-EPMC12907902","cross_references":{"pubmed":["41666678"],"doi":["10.1016/j.redox.2026.104075"]}}