{"doi":"10.1172/jci180282","title":"Sialylated glycoproteins suppress immune cell killing by binding to Siglec-7 and Siglec-9 in prostate cancer","abstract":"Prostate cancer is the second leading cause of male cancer death in the U.S. Current immune checkpoint inhibitor-based immunotherapies have improved survival for many malignancies; however, they have failed to prolong survival for prostate cancer. Siglecs (sialic acid-binding immunoglobulin-like lectins) are expressed on immune cells and regulate their function. Siglec-7 and Siglec-9 contribute to immune evasion in cancer by interacting with sialic acid-containing glycoprotein ligands on cancer cells. However, the role of Siglec-7/9 receptors and their ligands in prostate cancer remains poorly understood. Here, we find that Siglec-7 and Siglec-9 are associated with poor prognosis in patients with prostate cancer and are highly expressed in myeloid cells, including macrophages, in prostate tumor tissues. Siglec-7 and -9 ligands were expressed in prostate cancer cells and human prostate tumor tissues. Blocking the interactions between Siglec-7/9 and sialic acids inhibited prostate cancer xenograft growth and increased immune cell infiltration in humanized mice in vivo. Using a CRISPRi screen and mass spectrometry, we identified CD59 as a candidate Siglec-9 ligand in prostate cancer. The identification of Siglec-7 and -9 as potential therapeutic targets, including the CD59/Siglec-9 axis, opens up opportunities for immune-based interventions in prostate cancer.","journal":"Journal of Clinical Investigation","year":2024,"id":418580,"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":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9456,"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":562118,"name":"Jessica C. Stark","orcid":"0000-0003-3828-5438","position":1,"is_corresponding":false},{"id":984587,"name":"G. Edward Marti","orcid":"0000-0002-3390-436X","position":2,"is_corresponding":false},{"id":1207016,"name":"Zenghua Fan","orcid":"0000-0002-5119-5296","position":3,"is_corresponding":false},{"id":1199611,"name":"Aram Lyu","orcid":"0000-0003-3044-4887","position":4,"is_corresponding":false},{"id":821075,"name":"Fernando Jose Garcia Marques","orcid":null,"position":5,"is_corresponding":false},{"id":366919,"name":"Xiangyue Zhang","orcid":"0000-0002-4517-6777","position":6,"is_corresponding":false},{"id":218283,"name":"Nicholas M. Riley","orcid":"0000-0002-1536-2966","position":7,"is_corresponding":false},{"id":865138,"name":"Sarah M. Totten","orcid":null,"position":8,"is_corresponding":false},{"id":260480,"name":"Abel Bermudez","orcid":"0009-0002-3235-5538","position":9,"is_corresponding":false},{"id":260487,"name":"Rosalie Nolley","orcid":"0009-0004-7269-5443","position":10,"is_corresponding":false},{"id":424490,"name":"Hongjuan Zhao","orcid":"0000-0001-6083-0370","position":11,"is_corresponding":false},{"id":24099,"name":"Lawrence Fong","orcid":"0000-0002-6428-428X","position":12,"is_corresponding":false},{"id":14548,"name":"Edgar G. Engleman","orcid":"0000-0002-2096-9279","position":13,"is_corresponding":false},{"id":240820,"name":"Sharon J. Pitteri","orcid":"0000-0002-3119-873X","position":14,"is_corresponding":false},{"id":218284,"name":"Carolyn R. Bertozzi","orcid":"0000-0003-4482-2754","position":15,"is_corresponding":false},{"id":1826,"name":"James D. Brooks","orcid":"0000-0003-4521-7505","position":16,"is_corresponding":false},{"id":1207015,"name":"Ru M. Wen","orcid":"0000-0002-4141-7377","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:57:09.067930Z","pmid":"39436703","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":[]}