{"doi":"10.1016/j.ccell.2021.08.005","title":"Activating a collaborative innate-adaptive immune response to control metastasis","abstract":"Tumor-associated macrophages (TAMs) promote metastasis and inhibit T cells, but macrophages can be polarized to kill cancer cells. Macrophage polarization could thus be a strategy for controlling cancer. We show that macrophages from metastatic pleural effusions of breast cancer patients can be polarized to kill cancer cells with monophosphoryl lipid A (MPLA) and interferon (IFN) γ. MPLA + IFNγ injected intratumorally or intraperitoneally reduces primary tumor growth and metastasis in breast cancer mouse models, suppresses metastasis, and enhances chemotherapy response in an ovarian cancer model. Both macrophages and T cells are critical for the treatment's anti-metastatic effects. MPLA + IFNγ stimulates type I IFN signaling, reprograms CD206 + TAMs to inducible NO synthase (iNOS) + macrophages, and activates cytotoxic T cells through macrophage-secreted interleukin-12 (IL-12) and tumor necrosis factor alpha (TNFα). MPLA and IFNγ are used individually in clinical practice and together represent a previously unexplored approach for engaging a systemic anti-tumor immune response.","journal":"Cancer Cell","year":2021,"id":145964,"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":281,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"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":622031,"name":"Tim Kees","orcid":null,"position":1,"is_corresponding":false},{"id":620182,"name":"Ana S. Almeida","orcid":"0000-0001-8997-2639","position":2,"is_corresponding":false},{"id":620183,"name":"Bodu Liu","orcid":"0000-0003-2097-725X","position":3,"is_corresponding":false},{"id":105725,"name":"Xue‐Yan He","orcid":"0000-0001-5423-5997","position":4,"is_corresponding":false},{"id":105728,"name":"David Ng","orcid":"0000-0001-8584-7558","position":5,"is_corresponding":false},{"id":620184,"name":"Xiao Han","orcid":"0000-0002-4036-8710","position":6,"is_corresponding":false},{"id":236768,"name":"David L. Spector","orcid":"0000-0003-3614-4965","position":7,"is_corresponding":false},{"id":33525,"name":"Iain A. McNeish","orcid":"0000-0002-9387-7586","position":8,"is_corresponding":false},{"id":325359,"name":"Phyllis A. Gimotty","orcid":"0000-0002-3850-9799","position":9,"is_corresponding":false},{"id":245472,"name":"Sylvia Adams","orcid":"0000-0003-4737-1952","position":10,"is_corresponding":false},{"id":103961,"name":"Mikala Egeblad","orcid":"0000-0002-3371-1445","position":11,"is_corresponding":false},{"id":620181,"name":"Lijuan Sun","orcid":"0000-0003-0080-7886","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T23:42:18.947086Z","pmid":"34478639","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":[]}