特雷姆2
胶质瘤
癌症研究
小胶质细胞
髓样
免疫系统
脑瘤
生物
肿瘤进展
流式细胞术
免疫学
癌症
医学
病理
髓系细胞
炎症
遗传学
作者
Jiaying Zheng,Lingxiao Wang,Shunyi Zhao,Wenjing Zhang,Yuzhou Chang,Dale B. Bosco,Tao Huang,Aastha Dheer,Shan Gao,Shengze Xu,Katayoun Ayasoufi,Rawan Al‐kharboosh,Fangfang Qi,Manling Xie,Aaron J. Johnson,Haidong Dong,Alfredo Quiñones‐Hinojosa,Long–Jun Wu
出处
期刊:Neuro-oncology
[Oxford University Press]
日期:2023-11-06
被引量:3
标识
DOI:10.1093/neuonc/noad214
摘要
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.We studied the TREM2 expression profile in various patient tumor samples and conducted single-cell transcriptomic analysis in both glioblastoma patients and the GL261 mouse glioma model. We utilized multiple mouse glioma models and employed state-of-the-art techniques such as in vivo two-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.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 pre-clinical 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.Our study unveiled a previously unrecognized protective role of tumor-myeloid TREM2. Specifically, we found TREM2 enhance the phagocytosis of tumor cells and promote an immune response by facilitating MHCII-associated CD4+ T cell responses against gliomas.
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