Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, 300000, China.
Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin, China.
Neurosurg Rev. 2024 Aug 10;47(1):417. doi: 10.1007/s10143-024-02633-4.
Glioma, especially glioblastoma patients, present highly heterogeneous and immunosuppressive microenvironment, leading to their poor response to treatment and survival. Targeting the tumor microenvironment is considered a promising therapeutic strategy. M2 macrophages are highly infiltrated in glioma tissue, even up to 50% of the total number of bulk tissue cells. Here, we identified GPR65 as the hub gene of the M2 macrophage-related module in glioma through WGCNA analysis. The expression and prognosis analysis suggested that GPR65 was positively correlated with the malignancy and poor prognosis of glioma, and the heterogeneity analysis found that GPR65 was highly expressed in the vascular proliferation area of glioma, which matched the spatial expression characteristics of M2 macrophages. We further verified that GPR65 was highly expressed in macrophages but not tumor cells in the glioma microenvironment by single-cell data analysis and immunofluorescence. Most importantly, we found that inhibition of GPR65 was sufficient to reduce macrophages' polarization response to glioma cell and break the malignant cooperation with glioma cells. Our study reports the expression characteristics and malignant behavior of GPR65 in the glioma microenvironment, which provides a new alternative target of treatment to glioma microenvironment.
胶质瘤，尤其是胶质母细胞瘤患者，存在高度异质性和免疫抑制的微环境，导致其对治疗的反应和生存较差。靶向肿瘤微环境被认为是一种有前途的治疗策略。M2 巨噬细胞高度浸润于胶质瘤组织中，甚至高达总组织细胞数的 50%。在这里，我们通过 WGCNA 分析鉴定出 GPR65 是胶质瘤中与 M2 巨噬细胞相关模块的枢纽基因。表达和预后分析表明，GPR65 与胶质瘤的恶性程度和预后不良呈正相关，异质性分析发现 GPR65 在胶质瘤的血管增殖区域高表达，与 M2 巨噬细胞的空间表达特征相匹配。我们通过单细胞数据分析和免疫荧光进一步证实，GPR65 在胶质瘤微环境中的巨噬细胞中高表达，但在肿瘤细胞中不表达。最重要的是，我们发现抑制 GPR65 足以减少巨噬细胞对胶质瘤细胞的极化反应，并打破与胶质瘤细胞的恶性合作。我们的研究报告了 GPR65 在胶质瘤微环境中的表达特征和恶性行为，为胶质瘤微环境提供了一个新的治疗替代靶点。
