TIM-3/CD68 双高表达与脑胶质瘤：预后特征与潜在治疗策略。

TIM-3/CD68 double-high expression in Glioma: Prognostic characteristics and potential therapeutic approaches.

机构信息

Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, PR China; State Key Laboratory of Oncology in South China, Guangzhou, PR China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, PR China.

Department of Neurosurgery, Sun Yat-sen University Cancer Center, Guangzhou, PR China; State Key Laboratory of Oncology in South China, Guangzhou, PR China; Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, PR China.

出版信息

Int Immunopharmacol. 2024 Sep 30;139:112665. doi: 10.1016/j.intimp.2024.112665. Epub 2024 Jul 12.

DOI:10.1016/j.intimp.2024.112665

PMID:39002523

Abstract

BACKGROUND

Immunotherapy has revolutionized the treatment of various types of tumors, but there has been no breakthrough in the treatment of gliomas. The aim of this study is to discover valuable immunotherapy target in glioma, analyze its expression in glioma and the related microenvironment, explore potential immunotherapy strategies, and propose new possibilities for the treatment of gliomas.

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.

摘要

背景

免疫疗法已经彻底改变了各种类型肿瘤的治疗方法，但在治疗神经胶质瘤方面尚未取得突破。本研究旨在发现神经胶质瘤中有价值的免疫治疗靶点，分析其在神经胶质瘤及其相关微环境中的表达，探索潜在的免疫治疗策略，并为神经胶质瘤的治疗提出新的可能性。

方法

使用免疫组织化学（IHC）和多重荧光免疫组织化学（mIHC）分析了来自中山大学肿瘤防治中心（SYSUCC）的 187 名神经胶质瘤患者中常见免疫标志物和检查点的表达。使用中国神经胶质瘤基因组图谱（CGGA）单细胞测序数据库的生物信息学分析检查 TIM-3 在不同巨噬细胞中的表达。使用 Kaplan-Meier 曲线预测 TIM-3 和 CD68 高表达样本的预后价值。使用 R 包分析 TIM-3/CD68 双高表达样本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度表达的免疫检查点。与其他肿瘤不同，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患者生存不良，可能成为 IDH 突变型神经胶质瘤和 IDH 野生型低级别神经胶质瘤（LGG）神经胶质瘤的新升级标志物（P<0.01）。探索 TIM-3 抑制剂与 p38 MAPK 抑制剂的联合使用可能是未来 TIM-3/CD68 双高表达神经胶质瘤的潜在治疗方向。