{"doi":"10.1101/2023.06.14.545005","title":"Hyperglycosylation of prosaposin in tumor DCs promotes immune escape in cancer","abstract":"Tumors develop strategies to evade immunity by suppressing antigen presentation. Here, we show that prosaposin drives CD8 T cell-mediated tumor immunity and that its hyperglycosylation in tumor DCs leads to cancer immune escape. We found that lysosomal prosaposin 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, TGF-β induced hyperglycosylation of prosaposin and its subsequent secretion, which ultimately caused depletion of lysosomal saposins. In melanoma patients, we found similar prosaposin hyperglycosylation in tumor-associated DCs, and reconstitution with prosaposin rescued activation of tumor-infiltrating T cells. Targeting tumor DCs with recombinant prosaposin triggered cancer protection and enhanced immune checkpoint therapy. Our studies demonstrate a critical function of prosaposin in tumor immunity and escape and introduce a novel principle of prosaposin-based cancer immunotherapy. One Sentence Summary: Prosaposin facilitates antigen cross-presentation and tumor immunity and its hyperglycosylation leads to immune evasion.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":399822,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","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":473942,"name":"Qi Wan","orcid":"0000-0002-1327-9851","position":4,"is_corresponding":false},{"id":1176196,"name":"Jessica Kim","orcid":"0000-0001-9795-2275","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":465530,"name":"Pankaj Sharma","orcid":"0000-0002-9130-9235","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:20:00.023537Z","pmid":"37398287","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":[]}