{"doi":"10.1093/noajnl/vdaa065","title":"MerTK inhibition decreases immune suppressive glioblastoma-associated macrophages and neoangiogenesis in glioblastoma microenvironment","abstract":"BACKGROUND: Glioblastoma-associated macrophages and microglia (GAMs) are the predominant immune cells in the tumor microenvironment. Activation of MerTK, a receptor tyrosine kinase, polarizes GAMs to an immunosuppressive phenotype, promoting tumor growth. Here, the role of MerTK inhibition in the glioblastoma microenvironment is investigated in vitro and in vivo. METHODS: Effects of MRX-2843 in glioblastoma microenvironment regulation were determined in vitro by cell viability, cytokine array, in vitro tube formation, Western blotting, and wound healing assays. A syngeneic GL261 orthotopic glioblastoma mouse model was used to evaluate the survival benefit of MRX-2843 treatment. Multiplex fluorescent immunohistochemistry was used to evaluate the expression of CD206, an anti-inflammatory marker on GAMs, and angiogenesis in murine brain tumor tissues. RESULTS: MRX-2843 inhibited cell growth and induced apoptosis in human glioblastoma cells and decreased protein expression of phosphorylated MerTK, AKT, and ERK, which are essential for cell survival signaling. Interleukin-8 and C-C motif chemokine ligand 2, the pro-glioma and pro-angiogenic cytokines, were decreased by MRX-2843. Decreased vascular formation and numbers of immunosuppressive (CD206+) GAMs were observed following MRX-2843 treatment in vivo, suggesting that in addition to alleviating immunosuppression, MRX-2843 also inhibits neoangiogenesis in the glioma microenvironment. These results were supported by a prolonged survival in the syngeneic mouse orthotopic GL261 glioblastoma model following MRX-2843 treatment. CONCLUSION: Our findings suggest that MRX-2843 has a therapeutic benefit via promoting GAM polarization away from immunosuppressive condition, inhibiting neoangiogenesis in the glioblastoma microenvironment and inducing tumor cell death.","journal":"Neuro-Oncology Advances","year":2020,"id":75052,"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":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"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":232021,"name":"Madison Butler","orcid":"0000-0002-1031-2054","position":1,"is_corresponding":false},{"id":392223,"name":"Meili Zhang","orcid":"0000-0002-6970-6154","position":2,"is_corresponding":false},{"id":392224,"name":"Wei Zhang","orcid":"0000-0001-7800-3189","position":3,"is_corresponding":false},{"id":364668,"name":"Hua Song","orcid":"0000-0002-1857-2440","position":4,"is_corresponding":false},{"id":393850,"name":"Lee Hwang","orcid":null,"position":5,"is_corresponding":false},{"id":356751,"name":"Andy D. Tran","orcid":"0000-0002-2388-7121","position":6,"is_corresponding":false},{"id":393851,"name":"Ryan Bash","orcid":null,"position":7,"is_corresponding":false},{"id":393852,"name":"Allison N. Schorzman","orcid":null,"position":8,"is_corresponding":false},{"id":336429,"name":"Ying Pang","orcid":"0000-0001-6195-2150","position":9,"is_corresponding":false},{"id":393853,"name":"Guangyang Yu","orcid":null,"position":10,"is_corresponding":false},{"id":346805,"name":"William C. Zamboni","orcid":"0000-0002-8319-4482","position":11,"is_corresponding":false},{"id":392225,"name":"Xiaodong Wang","orcid":"0000-0003-3293-7538","position":12,"is_corresponding":false},{"id":392226,"name":"Stephen V. Frye","orcid":"0000-0002-2415-2215","position":13,"is_corresponding":false},{"id":393854,"name":"Christopher R. Miller","orcid":null,"position":14,"is_corresponding":false},{"id":331837,"name":"Dragan Maric","orcid":"0000-0003-2912-7921","position":15,"is_corresponding":false},{"id":372492,"name":"Masaki Terabe","orcid":"0000-0002-1777-0189","position":16,"is_corresponding":false},{"id":109755,"name":"Mark R. Gilbert","orcid":"0000-0003-2556-9722","position":17,"is_corresponding":false},{"id":304429,"name":"H. Shelton Earp","orcid":"0000-0003-1229-4619","position":18,"is_corresponding":false},{"id":232028,"name":"Jing Wu","orcid":"0000-0002-1686-9646","position":19,"is_corresponding":false},{"id":232023,"name":"Yuting Su","orcid":"0000-0001-5165-204X","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T21:46:33.313355Z","pmid":"32642716","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":[]}