{"doi":"10.1038/s41420-024-02027-x","title":"DRG2 is required for surface localization of PD-L1 and the efficacy of anti-PD-1 therapy","abstract":"More than half of tumor patients with high PD-L1 expression do not respond to anti-PD-1/PD-L1 therapy, and the underlying mechanisms are yet to be clarified. Here we show that developmentally regulated GTP-binding protein 2 (DRG2) is required for response of PD-L1-expressing tumors to anti-PD-1 therapy. DRG2 depletion enhanced IFN-γ signaling and increased the PD-L1 level in melanoma cells. However, it inhibited recycling of endosomal PD-L1 and reduced surface PD-L1 levels, which led to defects in interaction with PD-1. Anti-PD-1 did not expand effector-like T cells within DRG2-depleted tumors and failed to improve the survival of DRG2-depleted tumor-bearing mice. Cohort analysis revealed that patients bearing melanoma with low DRG2 protein levels were resistant to anti-PD-1 therapy. These findings identify DRG2 as a key regulator of recycling of endosomal PD-L1 and response to anti-PD-1 therapy and provide insights into how to increase the correlation between PD-L1 expression and response to anti-PD-1 therapy.","journal":"Cell Death Discovery","year":2024,"id":453659,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1276507,"name":"Muralidharan Mani","orcid":"0000-0002-1194-3616","position":1,"is_corresponding":false},{"id":504512,"name":"Jeonghwan Kim","orcid":"0000-0002-1697-5107","position":2,"is_corresponding":false},{"id":1276938,"name":"Wha Ja Cho","orcid":null,"position":3,"is_corresponding":false},{"id":1276508,"name":"Thomas F.J. Martin","orcid":"0000-0002-5204-0202","position":5,"is_corresponding":false},{"id":138908,"name":"Hun Su Chu","orcid":null,"position":6,"is_corresponding":false},{"id":1276939,"name":"Won Jin Jeong","orcid":null,"position":7,"is_corresponding":false},{"id":1276509,"name":"Byung Yong Ahn","orcid":"0000-0002-9871-5180","position":10,"is_corresponding":false},{"id":1276510,"name":"Byung Ju Lee","orcid":"0000-0001-5519-8884","position":11,"is_corresponding":false},{"id":1276940,"name":"Do Yong Jeon","orcid":null,"position":12,"is_corresponding":false},{"id":1276511,"name":"Jeong Woo Park","orcid":"0000-0002-3355-6908","position":13,"is_corresponding":false},{"id":349895,"name":"Junil Kim","orcid":"0000-0002-1202-1808","position":14,"is_corresponding":false},{"id":1276506,"name":"Seong Hee Choi","orcid":"0000-0003-2365-6187","position":0,"is_corresponding":true}],"reference_count":86,"raw_metadata":null,"created_at":"2026-07-19T02:03:03.428151Z","pmid":"38802348","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}