TREM2 mediates MHCII-associated CD4+ T-cell response against gliomas

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 · 发表于：Neuro-Oncology · 年份：2023 · DOI：10.1093/neuonc/noad214 · 被引用次数：23 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Inflammation biomarkers and pathways、Immune cells in cancer

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 a...