METHODS: Immunohistochemistry (IHC) and multiplex fluorescence immunohistochemistry (mIHC) were used to analyze the expression of common immune markers and checkpoints in 187 glioma patients from Sun Yat-sen University Caner Center (SYSUCC). Bioinformatics analysis was used to examine the expression of TIM-3 in different macrophages using the Chinese Glioma Genome Atlas (CGGA) single-cell sequencing database. The Kaplan-Meier curve was used to predict the prognostic value of samples with high TIM-3 and CD68 expression. The R package was used to analyze the somatic mutation status and the sensitivity of small molecule inhibitors in TIM-3/CD68 double-high expression samples.
RESULTS: TIM-3 is a relatively highly expressed immune checkpoint in glioma. Unlike other tumors, TIM-3 is mainly expressed on macrophages in the glioma microenvironment. TIM-3/CD68 double-high expression suggests poor survival in glioma and may be a new upgrade marker in both IDH-mutant glioma and IDH-wildtype low-grade glioma (LGG) glioma (P < 0.01). Exploring the combination of TIM-3 inhibitors and p38 MAPK inhibitor may be a potential treatment direction for TIM-3/CD68 double high expression gliomas in the future.
CONCLUSIONS: The combination of TIM-3 and CD68 holds significant importance as a potential target for both prognosis and therapeutic intervention in glioma.
方法:采用免疫组织化学(IHC)和多重荧光免疫组织化学(mIHC)分析了来自中山大学癌症中心(SYSUCC)的187例胶质瘤患者常见免疫标志物和检查点的表达。使用中国胶质瘤基因组图谱(CGGA)单细胞测序数据库,生物信息学分析用于检测TIM-3在不同巨噬细胞中的表达。Kaplan-Meier曲线用于预测具有高TIM-3和CD68表达的样品的预后价值。用R包分析TIM-3/CD68双高表达样品中的体细胞突变状态和小分子抑制剂的敏感性。
结果:TIM-3是神经胶质瘤中相对高表达的免疫检查点。不像其他肿瘤,TIM-3主要在神经胶质瘤微环境中的巨噬细胞上表达。TIM-3/CD68双高表达提示神经胶质瘤生存率低,可能是IDH突变型神经胶质瘤和IDH野生型低级别神经胶质瘤(LGG)神经胶质瘤的一个新的升级标记(P<0.01)。探索TIM-3抑制剂和p38MAPK抑制剂的联合应用可能是未来TIM-3/CD68双高表达胶质瘤的潜在治疗方向。
结论:TIM-3和CD68的联合作为神经胶质瘤预后和治疗干预的潜在靶点具有重要意义。