{"doi":"10.1093/neuonc/noad214","title":"TREM2 mediates MHCII-associated CD4+ T-cell response against gliomas","abstract":"BACKGROUND: Myeloid cells comprise up to 50% of the total tumor mass in glioblastoma (GBM) and have been implicated in promoting tumor progression and immunosuppression. Modulating the response of myeloid cells to the tumor has emerged as a promising new approach for cancer treatment. In this regard, we focus on the Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), which has recently emerged as a novel immune modulator in peripheral tumors. METHODS: We studied the TREM2 expression profile in various patient tumor samples and conducted single-cell transcriptomic analysis in both GBM patients and the GL261 mouse glioma model. We utilized multiple mouse glioma models and employed state-of-the-art techniques such as invivo 2-photon imaging, spectrum flow cytometry, and in vitro co-culture assays to study TREM2 function in myeloid cell-mediated phagocytosis of tumor cells, antigen presentation, and response of CD4+ T cells within the tumor hemispheres. RESULTS: Our research revealed significantly elevated levels of TREM2 expression in brain tumors compared to other types of tumors in patients. TREM2 was predominantly localized in tumor-associated myeloid cells and was highly expressed in nearly all microglia, as well as various subtypes of macrophages. Surprisingly, in preclinical glioma models, TREM2 deficiency did not confer a beneficial effect; instead, it accelerated glioma progression. Through detailed investigations, we determined that TREM2 deficiency impaired the ability of tumor-myeloid cells to phagocytose tumor cells and led to reduced expression of MHCII. This deficiency further significantly decreased the presence of CD4+ T cells within the tumor hemispheres. CONCLUSIONS: Our study unveiled a previously unrecognized protective role of tumor-myeloid TREM2. Specifically, we found that TREM2 enhances the phagocytosis of tumor cells and promotes an immune response by facilitating MHCII-associated CD4+ T-cell responses against gliomas.","journal":"Neuro-Oncology","year":2023,"id":328473,"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":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9643,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":660361,"name":"Lingxiao Wang","orcid":"0000-0001-5819-4563","position":1,"is_corresponding":false},{"id":689266,"name":"Shunyi Zhao","orcid":"0000-0001-7265-0801","position":2,"is_corresponding":false},{"id":548594,"name":"Wenjing Zhang","orcid":"0000-0001-6931-900X","position":3,"is_corresponding":false},{"id":95209,"name":"Yuzhou Chang","orcid":"0000-0003-4893-1886","position":4,"is_corresponding":false},{"id":258020,"name":"Dale B. Bosco","orcid":"0000-0002-3982-5056","position":5,"is_corresponding":false},{"id":1049904,"name":"Tao Huang","orcid":"0000-0003-2607-8407","position":6,"is_corresponding":false},{"id":559379,"name":"Aastha Dheer","orcid":"0000-0003-3289-1402","position":7,"is_corresponding":false},{"id":1049905,"name":"Shan Gao","orcid":"0000-0001-5010-8376","position":8,"is_corresponding":false},{"id":1049906,"name":"Shengze Xu","orcid":"0009-0005-7581-8012","position":9,"is_corresponding":false},{"id":256583,"name":"Katayoun Ayasoufi","orcid":"0000-0002-3797-0823","position":10,"is_corresponding":false},{"id":296992,"name":"Rawan Al‐kharboosh","orcid":null,"position":11,"is_corresponding":false},{"id":1017030,"name":"Fangfang Qi","orcid":"0000-0001-5719-3200","position":12,"is_corresponding":false},{"id":556049,"name":"Manling Xie","orcid":"0000-0002-1747-1699","position":13,"is_corresponding":false},{"id":256585,"name":"Aaron J. Johnson","orcid":"0000-0002-7921-484X","position":14,"is_corresponding":false},{"id":230198,"name":"Haidong Dong","orcid":"0000-0002-5782-2983","position":15,"is_corresponding":false},{"id":278684,"name":"Alfredo Quiñones‐Hinojosa","orcid":"0000-0003-4262-5968","position":16,"is_corresponding":false},{"id":258025,"name":"Long‐Jun Wu","orcid":"0000-0001-8019-3380","position":17,"is_corresponding":false},{"id":255100,"name":"Jiaying Zheng","orcid":"0000-0002-7457-6198","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T01:08:52.196069Z","pmid":"37941134","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":[]}