{"doi":"10.1101/2025.04.30.651522","title":"Anti-CSF-1R therapy with combined immuno- chemotherapy coordinate an adaptive immune response to eliminate macrophage enriched Triple Negative Breast Cancers","abstract":"ABSTRACT Patients diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory metronomic Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic syngeneic Trp53 null TNBC genetically engineered mouse models (GEMMs) that present with high macrophage infiltration. Mechanistically, CSF-1R inhibition along with CTX disrupted the M-CSF/CSF-1R axis which upregulated IL-17, IL-15 and type II interferon resulting in elevated B- and T cell infiltration. Addition of an anti-PD-1 maintenance dose helped overcome de novo PD-L1 intra-tumoral heterogeneity (ITH) associated recurrence in lung and liver mTNBC.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":557770,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"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":656870,"name":"Xueying Yuan","orcid":"0000-0001-6242-7630","position":1,"is_corresponding":false},{"id":1026981,"name":"Fengshuo Liu","orcid":"0000-0003-4651-7710","position":2,"is_corresponding":false},{"id":656471,"name":"Hilda L. Chan","orcid":"0000-0001-6882-4274","position":3,"is_corresponding":false},{"id":1458257,"name":"Christina Zhang","orcid":null,"position":4,"is_corresponding":false},{"id":310999,"name":"William Bowie","orcid":"0000-0002-5040-5562","position":5,"is_corresponding":false},{"id":719534,"name":"Alex J. Smith","orcid":"0009-0004-1168-0256","position":6,"is_corresponding":false},{"id":1044833,"name":"Sebastian J. Calderon","orcid":null,"position":7,"is_corresponding":false},{"id":1044832,"name":"Nadia Lieu","orcid":null,"position":8,"is_corresponding":false},{"id":621855,"name":"William Wu","orcid":"0000-0002-1179-3435","position":9,"is_corresponding":false},{"id":715397,"name":"Paul Porter","orcid":"0000-0001-9051-589X","position":10,"is_corresponding":false},{"id":394324,"name":"Poonam Sarkar","orcid":null,"position":11,"is_corresponding":false},{"id":656869,"name":"Na Zhao","orcid":"0000-0002-8161-3380","position":12,"is_corresponding":false},{"id":1458258,"name":"Constanze V. Oehler","orcid":null,"position":13,"is_corresponding":false},{"id":1458259,"name":"Ondrej Peller","orcid":null,"position":14,"is_corresponding":false},{"id":393497,"name":"M. Waleed Gaber","orcid":"0000-0002-6192-0367","position":15,"is_corresponding":false},{"id":18925,"name":"Qian Zhu","orcid":"0000-0001-7062-8221","position":16,"is_corresponding":false},{"id":1883,"name":"Charles M. Perou","orcid":"0000-0001-9827-2247","position":17,"is_corresponding":false},{"id":239995,"name":"Xiang H.-F. Zhang","orcid":"0000-0002-5674-8670","position":18,"is_corresponding":false},{"id":267159,"name":"Jeffrey M. Rosen","orcid":"0000-0002-6637-844X","position":19,"is_corresponding":false},{"id":857874,"name":"Diego A. Pedroza","orcid":"0000-0002-7355-2952","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T02:55:21.727661Z","pmid":"40568104","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":[]}