{"doi":"10.1126/sciadv.aaz8521","title":"Efficient blockade of locally reciprocated tumor-macrophage signaling using a TAM-avid nanotherapy","abstract":"Interpreting how multicellular interactions in the tumor affect resistance pathways to BRAF and MEK1/2 MAPK inhibitors (MAPKi) remains a challenge. To investigate this, we profiled global ligand-receptor interactions among tumor and stromal/immune cells from biopsies of MAPK-driven disease. MAPKi increased tumor-associated macrophages (TAMs) in some patients, which correlated with poor clinical response, and MAPKi coamplified bidirectional tumor-TAM signaling via receptor tyrosine kinases (RTKs) including AXL, MERTK, and their ligand GAS6. In xenograft tumors, intravital microscopy simultaneously monitored in situ single-cell activities of multiple kinases downstream of RTKs, revealing MAPKi increased TAMs and enhanced bypass signaling in TAM-proximal tumor cells. As a proof-of-principle strategy to block this signaling, we developed a multi-RTK kinase inhibitor nanoformulation that accumulated in TAMs and delayed disease progression. Thus, bypass signaling can reciprocally amplify across nearby cell types, offering new opportunities for therapeutic design.","journal":"Science Advances","year":2020,"id":97795,"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":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9619,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":362443,"name":"Ran Li","orcid":"0000-0002-8537-8824","position":1,"is_corresponding":false},{"id":381706,"name":"Thomas S.C. Ng","orcid":"0000-0002-3676-1800","position":2,"is_corresponding":false},{"id":362442,"name":"Gaurav Luthria","orcid":"0000-0002-7896-6134","position":3,"is_corresponding":false},{"id":248018,"name":"Madeleine J. Oudin","orcid":"0000-0001-6988-4260","position":4,"is_corresponding":false},{"id":362445,"name":"Mark Prytyskach","orcid":"0000-0001-7070-8993","position":5,"is_corresponding":false},{"id":362446,"name":"Rainer H. Köhler","orcid":"0000-0001-6269-6590","position":6,"is_corresponding":false},{"id":23522,"name":"Ralph Weissleder","orcid":"0000-0003-0828-4143","position":7,"is_corresponding":false},{"id":19320,"name":"Douglas A. Lauffenburger","orcid":"0000-0002-0050-989X","position":8,"is_corresponding":false},{"id":362448,"name":"Miles A. Miller","orcid":"0000-0001-7638-8898","position":9,"is_corresponding":false},{"id":484017,"name":"Stephanie J. Wang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T22:36:02.818637Z","pmid":"32494745","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":[]}