{"doi":"10.1093/neuonc/noad257","title":"Triggering receptor expressed on myeloid cells 2 (TREM2) regulates phagocytosis in glioblastoma","abstract":"BACKGROUND: Glioblastomas (GBMs) are central nervous system tumors that resist standard-of-care interventions and even immune checkpoint blockade. Myeloid cells in the tumor microenvironment can contribute to GBM progression; therefore, emerging immunotherapeutic approaches include reprogramming these cells to achieve desirable antitumor activity. Triggering receptor expressed on myeloid cells 2 (TREM2) is a myeloid signaling regulator that has been implicated in a variety of cancers and neurological diseases with contrasting functions, but its role in GBM immunopathology and progression is still under investigation. METHODS: Our reverse translational investigations leveraged single-cell RNA sequencing and cytometry of human gliomas to characterize TREM2 expression across myeloid subpopulations. Using 2 distinct murine glioma models, we examined the role of Trem2 on tumor progression and immune modulation of myeloid cells. Furthermore, we designed a method of tracking phagocytosis of glioma cells in vivo and employed in vitro assays to mechanistically understand the influence of TREM2 signaling on tumor uptake. RESULTS: We discovered that TREM2 expression does not correlate with immunosuppressive pathways, but rather showed strong a positive association with the canonical phagocytosis markers lysozyme (LYZ) and macrophage scavenger receptor (CD163) in gliomas. While Trem2 deficiency was found to be dispensable for gliomagenesis, Trem2+ myeloid cells display enhanced tumor uptake compared to Trem2- cells. Mechanistically, we demonstrate that TREM2 mediates phagocytosis via Syk signaling. CONCLUSIONS: These results indicate that TREM2 is not associated with immunosuppression in gliomas. Instead, TREM2 is an important regulator of phagocytosis that may be exploited as a potential therapeutic strategy for brain tumors.","journal":"Neuro-Oncology","year":2024,"id":418303,"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":52,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"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":351004,"name":"Pravesh Gupta","orcid":"0000-0002-1643-8950","position":1,"is_corresponding":false},{"id":991153,"name":"Shivangi Oberai","orcid":"0009-0009-3480-2101","position":2,"is_corresponding":false},{"id":1162517,"name":"Rakesh Trivedi","orcid":"0000-0003-4835-1814","position":3,"is_corresponding":false},{"id":1205804,"name":"Hiroshi Katayama","orcid":"0000-0002-9735-6630","position":4,"is_corresponding":false},{"id":1162984,"name":"Prashanth Chakrapani","orcid":null,"position":5,"is_corresponding":false},{"id":554753,"name":"Minghao Dang","orcid":"0000-0001-7287-2877","position":6,"is_corresponding":false},{"id":806469,"name":"Simona Migliozzi","orcid":"0000-0002-4870-8943","position":7,"is_corresponding":false},{"id":622340,"name":"Joy Gumin","orcid":null,"position":8,"is_corresponding":false},{"id":1206632,"name":"Divya B Kadri","orcid":null,"position":9,"is_corresponding":false},{"id":1206633,"name":"Jessica K. 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Huse","orcid":"0000-0003-4514-0640","position":16,"is_corresponding":false},{"id":51782,"name":"Antonio Iavarone","orcid":"0000-0002-0683-4634","position":17,"is_corresponding":false},{"id":14192,"name":"Linghua Wang","orcid":"0000-0001-9380-0266","position":18,"is_corresponding":false},{"id":232776,"name":"Karen Clise-Dwyer","orcid":"0000-0001-9954-1197","position":19,"is_corresponding":false},{"id":254083,"name":"Krishna Bhat","orcid":"0000-0002-2020-8509","position":20,"is_corresponding":false},{"id":991154,"name":"Mekenzie Peshoff","orcid":"0000-0003-2678-5400","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-19T01:57:02.483590Z","pmid":"38237157","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":[]}