{"doi":"10.1016/j.intimp.2025.114906","title":"Targeting SPP1+ macrophages via the SPP1-CD44 axis reveals a key mechanism of immune suppression and tumor progression in ovarian cancer","abstract":null,"journal":"International Immunopharmacology","year":2025,"id":609989,"datarank":0.5533319181170905,"base_score":3.6888794541139363,"endowment":3.6888794541139363,"self_citation_contribution":0.5533319181170905,"citation_network_contribution":0.0,"self_endowment_contribution":0.5533319181170905,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":269935,"name":"Mei Jiang","orcid":"0000-0002-9111-0410","position":1,"is_corresponding":false},{"id":544134,"name":"Yue Li","orcid":"0000-0003-2991-970X","position":2,"is_corresponding":false},{"id":353750,"name":"Jin Cheng","orcid":"0000-0002-4364-9657","position":3,"is_corresponding":false},{"id":1361133,"name":"Fei Liu","orcid":"0000-0003-1746-8454","position":4,"is_corresponding":false},{"id":1568096,"name":"Xiaoyang Han","orcid":null,"position":5,"is_corresponding":false},{"id":1083751,"name":"Jiahao Guo","orcid":"0000-0002-2424-6983","position":6,"is_corresponding":false},{"id":1406272,"name":"Lei Feng","orcid":"0000-0001-5703-5923","position":7,"is_corresponding":false},{"id":513878,"name":"Zhefeng Li","orcid":"0000-0002-2874-2853","position":8,"is_corresponding":false},{"id":1568097,"name":"Junjie Yi","orcid":null,"position":9,"is_corresponding":false},{"id":1568099,"name":"Xiaoting Zhao","orcid":null,"position":10,"is_corresponding":false},{"id":416216,"name":"Yan Gao","orcid":"0000-0003-0122-1561","position":11,"is_corresponding":false},{"id":1568101,"name":"Wentao Yue","orcid":null,"position":12,"is_corresponding":false},{"id":1568095,"name":"Lisha Hou","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Targeting SPP1+ macrophages via the SPP1-CD44 axis reveals a key mechanism of immune suppression and tumor progression in ovarian cancer","abstract":"Tumor-associated macrophages (TAMs) play a pivotal role in immune suppression, tumor progression, and metastasis within the tumor microenvironment (TME) of ovarian cancer. While TAMs are known to promote T-cell dysfunction, the precise molecular mechanisms governing this process remain poorly understood. Here, we performed an integrated analysis of six high-grade serous ovarian cancer (HGSOC) single-cell sequencing datasets to investigate the molecular and functional diversity of TAMs in HGSOC. We identified an SPP1 + TAM subpopulation enriched in HGSOC and strongly associated with poor prognosis. These macrophages promoted T-cell exhaustion via the SPP1-CD44 axis, which emerged as the principal mediator of immune suppression. Functional assays demonstrated that SPP1 secreted by TAMs drove T-cell exhaustion, weakening anti-tumor immunity. Blocking either SPP1 or CD44 effectively reversed T-cell exhaustion, restored CD8 + T-cell functionality, and suppressed tumor growth in vivo . Furthermore, molecular docking and dynamics simulations identified nilotinib as a potential SPP1 inhibitor, exhibiting strong binding affinity and stability. In vitro assays confirmed that nilotinib reduced PD-1 expression in Jurkat cells induced by M2-type macrophages, underscoring its therapeutic potential in reversing T-cell exhaustion in ovarian cancer. The research demonstrates that SPP1 + TAMs drive immune suppression and T-cell exhaustion in ovarian cancer via the SPP1-CD44 axis, highlighting this pathway as a promising therapeutic target for reprogramming the immune microenvironment and improving patient outcomes.","is_dataset_classified":null,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40446696","pmcid":null,"openalex_id":"https://openalex.org/W4410892762","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"82373397","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82403937","title":null},{"funder_name":"Capital Medical University","grant_id":"","title":null}],"total_grants":3,"fwci":14.4088,"citation_percentile":0.99321034,"influential_citations":0,"citation_trend":[{"year":2025,"count":11},{"year":2026,"count":26}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1016/j.intimp.2025.114906","host_type":"journal"},{"url":"https://doi.org/10.1016/j.intimp.2025.114906","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1567576925008963?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1567576925008963?httpAccept=text/plain","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40446696","host_type":"repository"}],"fields_of_study":["Immune cells in cancer","Galectins and Cancer Biology","Phagocytosis and Immune Regulation"],"mesh_terms":["Tumor-Associated Macrophages","Animals","Female","Humans","Macrophages","Ovarian Neoplasms","Pyrimidines","CD8-Positive T-Lymphocytes","Disease Progression","Hyaluronan Receptors","Jurkat Cells","Cell Line, Tumor","Mice","Osteopontin","Tumor Microenvironment"],"keywords":["Mechanism (biology)","Cancer research","Immune system","Ovarian cancer","CD44","Medicine","Cancer","Key (lock)","Immunology","Biology","Internal medicine","Physics","Cell","immunosuppression","Single-cell Analysis","Cd8(+) T-cell Exhaustion","Spp1(+) Tams"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T18:17:47.435367Z","pmid":null,"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":[]}