{"doi":"10.1073/pnas.2015024118","title":"Genome-wide CRISPR screens reveal a specific ligand for the glycan-binding immune checkpoint receptor Siglec-7","abstract":", molecules that inhibit immune cell activity following binding to glycosylated cell-surface antigens, are emerging as attractive targets for cancer immunotherapy. Defining biologically relevant ligands that bind and activate such receptors, however, has historically been a significant challenge. Here, we present a CRISPRi genomic screening strategy that allowed unbiased identification of the key genes required for cell-surface presentation of glycan ligands on leukemia cells that bind the glyco-immune checkpoint receptors Siglec-7 and Siglec-9. This approach revealed a selective interaction between Siglec-7 and the mucin-type glycoprotein CD43. Further work identified a specific N-terminal glycopeptide region of CD43 containing clusters of disialylated O-glycan tetrasaccharides that form specific Siglec-7 binding motifs. Knockout or blockade of CD43 in leukemia cells relieves Siglec-7-mediated inhibition of immune killing activity. This work identifies a potential target for immune checkpoint blockade therapy and represents a generalizable approach to dissection of glycan-receptor interactions in living cells.","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":147568,"datarank":0.7565137675378871,"base_score":5.043425116919247,"endowment":5.043425116919247,"self_citation_contribution":0.7565137675378871,"citation_network_contribution":0.0,"self_endowment_contribution":0.7565137675378871,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":154,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":627868,"name":"Leonhard Möckl","orcid":"0000-0003-1387-886X","position":1,"is_corresponding":false},{"id":259930,"name":"Stacy A. Malaker","orcid":"0000-0003-2382-5067","position":2,"is_corresponding":false},{"id":218280,"name":"Kayvon Pedram","orcid":"0000-0001-8365-1826","position":3,"is_corresponding":false},{"id":62605,"name":"Gaelen T. Hess","orcid":"0000-0002-3836-0277","position":4,"is_corresponding":false},{"id":218283,"name":"Nicholas M. Riley","orcid":"0000-0002-1536-2966","position":5,"is_corresponding":false},{"id":266120,"name":"Melissa A. Gray","orcid":"0000-0002-7700-1090","position":6,"is_corresponding":false},{"id":615436,"name":"Benjamin Smith","orcid":"0000-0001-8802-416X","position":7,"is_corresponding":false},{"id":62612,"name":"Michael C. Bassik","orcid":"0000-0001-5185-8427","position":8,"is_corresponding":false},{"id":270551,"name":"W. E. Moerner","orcid":"0000-0002-2830-209X","position":9,"is_corresponding":false},{"id":218284,"name":"Carolyn R. Bertozzi","orcid":"0000-0003-4482-2754","position":10,"is_corresponding":false},{"id":218281,"name":"Simon Wisnovsky","orcid":"0000-0003-4010-4309","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:42:35.448762Z","pmid":"33495350","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":[]}