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.
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：免疫疗法彻底改变了各种类型肿瘤的治疗方法，但是在治疗神经胶质瘤方面没有取得突破。本研究的目的是发现有价值的脑胶质瘤免疫治疗靶点,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，并提出治疗神经胶质瘤的新可能性。
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。
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。
