骨髓细胞占胶质母细胞瘤 (GBM) 肿瘤总质量的 50%，与促进肿瘤进展和免疫抑制有关。调节骨髓细胞对肿瘤的反应已成为一种有前途的癌症治疗新方法。在这方面，我们重点关注骨髓细胞表达的触发受体2（TREM2），它最近作为外周肿瘤中的新型免疫调节剂出现。我们研究了各种患者肿瘤样本中的TREM2表达谱，并进行了单细胞转录组分析在胶质母细胞瘤患者和 GL261 小鼠胶质瘤模型中。我们利用多种小鼠神经胶质瘤模型，并采用体内双光子成像、光谱流式细胞术和体外共培养测定等最先进的技术来研究 TREM2 在骨髓细胞介导的肿瘤细胞吞噬作用中的功能，抗原呈递以及肿瘤半球内 CD4 T 细胞的反应。我们的研究表明，与患者其他类型的肿瘤相比，脑肿瘤中 TREM2 的表达水平显着升高。 TREM2 主要位于肿瘤相关骨髓细胞中，并且在几乎所有小胶质细胞以及巨噬细胞的各种亚型中高表达。令人惊讶的是，在临床前神经胶质瘤模型中，TREM2 缺陷并没有带来有益的效果；相反，它加速了神经胶质瘤的进展。通过详细研究，我们确定TREM2缺陷损害了肿瘤骨髓细胞吞噬肿瘤细胞的能力，并导致MHCII表达减少。这种缺陷进一步显着减少了肿瘤半球内 CD4 T 细胞的存在。我们的研究揭示了肿瘤骨髓 TREM2 以前未被认识到的保护作用。具体来说，我们发现 TREM2 增强肿瘤细胞的吞噬作用，并通过促进 MHCII 相关的 CD4 T 细胞针对神经胶质瘤的反应来促进免疫反应。© 作者 2023。由牛津大学出版社代表神经肿瘤学会出版。版权所有。如需权限，请发送电子邮件至：journals.permissions@oup.com。

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.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.