{"doi":"10.1016/j.celrep.2025.115676","title":"Semaphorin7A and PD-L1 cooperatively drive immunosuppression during mammary involution and breast cancer","abstract":"Postpartum mammary gland remodeling after a pregnancy/lactation cycle is characterized by mechanisms of cell death and inflammation. Here, we show that SEMA7A promotes PD-L1 expression in immune cells of the mammary tissue during involution. These same phenotypes are mimicked in the microenvironment of SEMA7A-expressing tumors, which partially respond to αPD-1/αPD-L1 treatments in vivo. However, cells that remain after treatment are enriched for SEMA7A expression. Therefore, we tested a monoclonal antibody that directly targets SEMA7A-expressing tumors, in part, by reducing SEMA7A-mediated upregulation of PD-L1. In vivo, the SEMA7A monoclonal antibody reduces tumor growth and/or promotes complete regression of mouse mammary tumors, reduces some immunosuppressive phenotypes in the tumor microenvironment, and restores cytotoxic T cells, suggesting that SEMA7A may be a candidate for immune-based therapy for breast cancer patients.","journal":"Cell Reports","year":2025,"id":532334,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1413913,"name":"Heather R. Fairchild","orcid":null,"position":1,"is_corresponding":false},{"id":1413515,"name":"Kelsey Kines","orcid":"0000-0002-3296-802X","position":2,"is_corresponding":false},{"id":396430,"name":"Lauren Cozzens","orcid":null,"position":3,"is_corresponding":false},{"id":1413914,"name":"Alexandria R Becks","orcid":null,"position":4,"is_corresponding":false},{"id":310833,"name":"Jill E. Slansky","orcid":"0000-0003-3820-1724","position":5,"is_corresponding":false},{"id":692159,"name":"Steven M. Anderson","orcid":"0000-0001-8667-7319","position":6,"is_corresponding":false},{"id":251811,"name":"Traci R. Lyons","orcid":"0000-0002-8876-0391","position":7,"is_corresponding":false},{"id":714471,"name":"Alan M. Elder","orcid":"0000-0002-0386-1792","position":0,"is_corresponding":true}],"reference_count":119,"raw_metadata":null,"created_at":"2026-07-19T02:51:23.237536Z","pmid":"40333186","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":[]}