中山大学附属第一医院Nu Zhang和北京大学Fan Bai共同合作，近期取得重要工作进展。他们研究提出了TREM2在中枢神经系统癌症和外周肿瘤中的不同作用。相关研究成果2024年5月23日在线发表于《癌细胞》杂志上。

据介绍，胶质母细胞瘤（GBM）是一种无法治愈的中枢神经系统（CNS）癌症，其特征是大量骨髓细胞浸润。在外周非CNS癌症中确定的髓系细胞定向治疗靶点是否适用于GBM需要进一步研究。

研究人员发现外周癌的关键免疫抑制靶点，触发骨髓细胞表达受体2（TREM2），对GBM具有免疫保护作用。遗传或药理学TREM2缺乏促进GBM在体内的进展。单细胞和空间测序揭示了GBM浸润的髓系细胞中TREM2的下调。TREM2与GBM中免疫抑制性骨髓和T细胞耗竭信号呈负相关。研究人员进一步证明，在GBM进展过程中，富含CNS的鞘脂与骨髓细胞上的TREM2结合，并引发抗肿瘤反应。临床上，骨髓细胞中TREM2的高表达与GBM的更好存活率相关。腺相关病毒介导的TREM2过表达阻碍GBM的进展，并与抗PD-1治疗协同作用。

总之。这一研究结果揭示了TREM2在CNS癌症中的不同功能，并支持癌症免疫疗法中的器官特异性髓细胞重塑。

附：英文原文

Title: Distinct roles of TREM2 in central nervous system cancers and peripheral cancers

Author: Jian Zhong, Xudong Xing, Yixin Gao, Lei Pei, Chenfei Lu, Huixin Sun, Yanxing Lai, Kang Du, Feizhe Xiao, Ying Yang, Xiuxing Wang, Yu Shi, Fan Bai, Nu Zhang

Issue&Volume: 2024-05-23

Abstract: Glioblastomas (GBM) are incurable central nervous system (CNS) cancers characterizedby substantial myeloid cell infiltration. Whether myeloid cell-directed therapeutictargets identified in peripheral non-CNS cancers are applicable to GBM requires furtherstudy. Here, we identify that the critical immunosuppressive target in peripheralcancers, triggering receptor expressed on myeloid cells-2 (TREM2), is immunoprotectivein GBM. Genetic or pharmacological TREM2 deficiency promotes GBM progression in vivo. Single-cell and spatial sequencing reveals downregulated TREM2 in GBM-infiltratedmyeloid cells. TREM2 negatively correlates with immunosuppressive myeloid and T cellexhaustion signatures in GBM. We further demonstrate that during GBM progression,CNS-enriched sphingolipids bind TREM2 on myeloid cells and elicit antitumor responses.Clinically, high TREM2 expression in myeloid cells correlates with better survivalin GBM. Adeno-associated virus-mediated TREM2 overexpression impedes GBM progressionand synergizes with anti-PD-1 therapy. Our results reveal distinct functions of TREM2in CNS cancers and support organ-specific myeloid cell remodeling in cancer immunotherapy.

DOI: 10.1016/j.ccell.2024.05.001

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00162-4