{"doi":"10.1126/science.adg1955","title":"Hyperglycosylation of prosaposin in tumor dendritic cells drives immune escape","abstract":"Tumors develop strategies to evade immunity by suppressing antigen presentation. In this work, we show that prosaposin (pSAP) drives CD8 T cell-mediated tumor immunity and that its hyperglycosylation in tumor dendritic cells (DCs) leads to cancer immune escape. We found that lysosomal pSAP and its single-saposin cognates mediated disintegration of tumor cell-derived apoptotic bodies to facilitate presentation of membrane-associated antigen and T cell activation. In the tumor microenvironment, transforming growth factor-β (TGF-β) induced hyperglycosylation of pSAP and its subsequent secretion, which ultimately caused depletion of lysosomal saposins. pSAP hyperglycosylation was also observed in tumor-associated DCs from melanoma patients, and reconstitution with pSAP rescued activation of tumor-infiltrating T cells. Targeting DCs with recombinant pSAP triggered tumor protection and enhanced immune checkpoint therapy. Our studies demonstrate a critical function of pSAP in tumor immunity and may support its role in immunotherapy.","journal":"Science","year":2024,"id":417337,"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":72,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"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":329072,"name":"Xiaolong Zhang","orcid":"0000-0002-9423-1461","position":1,"is_corresponding":false},{"id":231031,"name":"Kévin Ly","orcid":"0000-0003-0729-3953","position":2,"is_corresponding":false},{"id":680625,"name":"Ji Hyung Kim","orcid":"0000-0001-6785-2345","position":3,"is_corresponding":false},{"id":1202902,"name":"Qi Wan","orcid":"0000-0002-0816-7855","position":4,"is_corresponding":false},{"id":1040343,"name":"Jessica Kim","orcid":"0000-0002-6717-1934","position":5,"is_corresponding":false},{"id":1041011,"name":"Mumeng Lou","orcid":null,"position":6,"is_corresponding":false},{"id":1076795,"name":"Lisa Kain","orcid":"0000-0001-5873-8647","position":7,"is_corresponding":false},{"id":91049,"name":"Luc Teyton","orcid":"0000-0002-4049-1583","position":8,"is_corresponding":false},{"id":1040344,"name":"Florian Winau","orcid":"0000-0002-6825-1442","position":9,"is_corresponding":false},{"id":1202901,"name":"Pankaj Sharma","orcid":"0000-0002-8361-8679","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:56:50.743370Z","pmid":"38207022","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":[]}