{"doi":"10.1084/jem.20240957","title":"Targeting CD206+ macrophages disrupts the establishment of a key antitumor immune axis","abstract":"CD206 is a common marker of a putative immunosuppressive \"M2\" state in tumor-associated macrophages (TAMs). We made a novel conditional CD206 (Mrc1) knock-in mouse to specifically visualize and/or deplete CD206+ TAMs. Early depletion of CD206+ macrophages and monocytes (Mono/Macs) led to the indirect loss of conventional type I dendritic cells (cDC1), CD8 T cells, and NK cells in tumors. CD206+ TAMs robustly expressed CXCL9, contrasting with stress-responsive Spp1-expressing TAMs and immature monocytes, which became prominent with early depletion. CD206+ TAMs differentially attracted activated CD8 T cells, and the NK and CD8 T cells in CD206-depleted tumors were deficient in Cxcr3 and cDC1-supportive Xcl1 and Flt3l expressions. Disrupting this key antitumor axis decreased tumor control by antigen-specific T cells in mice. In human cancers, a CD206Replete, but not a CD206Depleted Mono/Mac gene signature correlated robustly with CD8 T cell, cDC1, and NK signatures and was associated with better survival. These findings negate the unqualified classification of CD206+ \"M2-like\" macrophages as immunosuppressive.","journal":"The Journal of Experimental Medicine","year":2024,"id":419042,"datarank":1.029809081446072,"base_score":3.828641396489095,"endowment":3.828641396489095,"self_citation_contribution":0.5742962094733643,"citation_network_contribution":0.4555128719727077,"self_endowment_contribution":0.5742962094733643,"citer_contribution":0.4555128719727077,"corpus_percentile":null,"corpus_rank":null,"citation_count":45,"citer_count":43,"citers_with_citation_signal":28,"citers_with_endowment":28,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"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":553724,"name":"Kenneth H. Hu","orcid":"0000-0002-0294-0202","position":1,"is_corresponding":false},{"id":811556,"name":"Kelly Kersten","orcid":"0000-0001-7615-2594","position":2,"is_corresponding":false},{"id":553723,"name":"Tristan Courau","orcid":"0000-0003-1819-9516","position":3,"is_corresponding":false},{"id":332080,"name":"Nicholas F. Kuhn","orcid":"0000-0001-5634-0846","position":4,"is_corresponding":false},{"id":1162897,"name":"Itzia Zaleta-Linares","orcid":null,"position":5,"is_corresponding":false},{"id":620243,"name":"Bushra Samad","orcid":"0000-0002-2893-0897","position":6,"is_corresponding":false},{"id":553722,"name":"Alexis J. Combes","orcid":"0000-0002-9110-6542","position":7,"is_corresponding":false},{"id":240181,"name":"Matthew F. Krummel","orcid":"0000-0001-7915-3533","position":8,"is_corresponding":false},{"id":553725,"name":"Arja Ray","orcid":"0000-0003-2305-2324","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:57:14.586331Z","pmid":"39601781","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":[]}