{"doi":"10.1172/jci.insight.138581","title":"Polymorphonuclear myeloid-derived suppressor cells limit antigen cross-presentation by dendritic cells in cancer","abstract":"DCs are a critical component of immune responses in cancer primarily due to their ability to cross-present tumor-associated antigens. Cross-presentation by DCs in cancer is impaired, which may represent one of the obstacles for the success of cancer immunotherapies. Here, we report that polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) blocked cross-presentation by DCs without affecting direct presentation of antigens by these cells. This effect did not require direct cell-cell contact and was associated with transfer of lipids. Neutrophils (PMN) and PMN-MDSC transferred lipid to DCs equally well; however, PMN did not affect DC cross-presentation. PMN-MDSC generate oxidatively truncated lipids previously shown to be involved in impaired cross-presentation by DCs. Accumulation of oxidized lipids in PMN-MDSC was dependent on myeloperoxidase (MPO). MPO-deficient PMN-MDSC did not affect cross-presentation by DCs. Cross-presentation of tumor-associated antigens in vivo by DCs was improved in MDSC-depleted or tumor-bearing MPO-KO mice. Pharmacological inhibition of MPO in combination with checkpoint blockade reduced tumor progression in different tumor models. These data suggest MPO-driven lipid peroxidation in PMN-MDSC as a possible non-cell autonomous mechanism of inhibition of antigen cross-presentation by DCs and propose MPO as potential therapeutic target to enhance the efficacy of current immunotherapies for patients with cancer.","journal":"JCI Insight","year":2020,"id":51687,"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":150,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.951,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":110056,"name":"Vladimir A. Tyurin","orcid":"0000-0002-3474-1697","position":1,"is_corresponding":false},{"id":110049,"name":"Yulia Y. Tyurina","orcid":"0000-0003-0287-2091","position":2,"is_corresponding":false},{"id":256196,"name":"Evgenii N. Tcyganov","orcid":"0000-0001-8605-7291","position":3,"is_corresponding":false},{"id":258869,"name":"Laxminarasimha Donthireddy","orcid":"0000-0003-0457-8486","position":4,"is_corresponding":false},{"id":110071,"name":"Valerian E. Kagan","orcid":"0000-0002-7245-1885","position":5,"is_corresponding":false},{"id":110069,"name":"Dmitry I. Gabrilovich","orcid":"0000-0001-9913-6407","position":6,"is_corresponding":false},{"id":258870,"name":"Filippo Veglia","orcid":"0000-0001-6710-1584","position":7,"is_corresponding":false},{"id":258868,"name":"Alessio Ugolini","orcid":"0000-0002-5970-9693","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-18T20:41:30.009880Z","pmid":"32584791","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":[]}