胶质瘤中 TIM-3/CD68 双高表达:预后特征和潜在的治疗方法。
TIM-3/CD68 double-high expression in Glioma: Prognostic characteristics and potential therapeutic approaches.
发表日期:2024 Jul 12
作者:
Wanming Hu, Depei Li, Yuanzhong Yang, Yongqiang Zheng, Jing Zeng, Ke Sai
来源:
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要:
免疫疗法彻底改变了各类肿瘤的治疗,但神经胶质瘤的治疗尚未取得突破。本研究的目的是发现胶质瘤中有价值的免疫治疗靶点,分析其在胶质瘤及相关微环境中的表达,探索潜在的免疫治疗策略,为胶质瘤的治疗提出新的可能性。免疫组织化学(IHC)和多重荧光免疫组织化学(mIHC)方法对中山大学肿瘤防治中心(SYSUCC)187例胶质瘤患者的常见免疫标志物和检查点的表达进行分析。使用中国胶质瘤基因组图谱(CGGA)单细胞测序数据库,通过生物信息学分析检查不同巨噬细胞中TIM-3的表达。 Kaplan-Meier曲线用于预测TIM-3和CD68高表达样本的预后价值。利用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。TIM-3是胶质瘤中表达相对高的免疫检查点。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 双高表达表明胶质瘤的生存率较差,可能是 IDH 突变型胶质瘤和 IDH 野生型低级别胶质瘤 (LGG) 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。TIM-3与CD68联合作为两者预后的潜在靶点具有重要意义和神经胶质瘤的治疗干预。版权所有 © 2024 Elsevier B.V. 保留所有权利。
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.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.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.The combination of TIM-3 and CD68 holds significant importance as a potential target for both prognosis and therapeutic intervention in glioma.Copyright © 2024 Elsevier B.V. All rights reserved.