文章：

IDH突变型胶质瘤新兴免疫治疗策略综述

A Review of Emerging Immunotherapeutic Strategies for IDH-Mutant Glioma

原文发布日期：27 June 2025

DOI: 10.3390/cancers17132178

类型: Article

开放获取: 是

英文摘要：

IDH-mutant gliomas (IMGs) are a unique subset of diffuse gliomas that follow a relatively indolent course compared to IDH-wildtype glioblastoma (GBM) but inevitably progress, often to a higher histologic grade. Current standard therapies, including surgery, chemoradiation, and the recently approved mutant IDH inhibitor (mIDHi) vorasidenib, provide limited disease control and are not curative. Given the immunosuppressive tumor microenvironment (TME) driven by the mutant IDH enzyme and its associated oncometabolite 2-hydroxyglutarate (2-HG), novel immunotherapies offer a promising avenue for treatment. The goal of this paper is to review the main immunologic characteristics that distinguish IMG from GBM, including reduced T cell infiltration and function, fewer myeloid cells, and increased immune-dampening signaling. We also evaluate the preclinical and clinical evidence for immunotherapeutic approaches with the most potential to induce meaningful clinical activity, such as immune checkpoint inhibitors, CAR T cells, tumor vaccines, myeloid redirection, and oncolytic viruses. Despite significant advances in immunotherapy for IMG, fundamental questions persist, including optimal timing and combination strategies, mechanisms underpinning treatment resistance, and strategies to overcome the suppressive microenvironment. Future exploration of these treatment modalities, with a focus on mitigating soluble immunosuppressive factors in the TME, enhancing in situ T cell persistence, and leveraging novel antigen targets, is critical for advancing the state of therapy for this presently incurable group of tumors.

摘要翻译： 

IDH突变型胶质瘤（IMGs）是弥漫性胶质瘤中一个独特的亚型，与IDH野生型胶质母细胞瘤（GBM）相比病程相对惰性，但最终仍会进展，且常发展为更高组织学级别。目前的标准治疗手段（包括手术、放化疗及近期获批的突变IDH抑制剂vorasidenib）对疾病控制有限且无法根治。鉴于突变IDH酶及其相关致癌代谢物2-羟基戊二酸（2-HG）驱动的免疫抑制性肿瘤微环境（TME），新型免疫疗法为治疗提供了前景广阔的途径。本文旨在综述IMGs区别于GBM的主要免疫学特征，包括T细胞浸润与功能减弱、髓系细胞减少及免疫抑制信号增强。同时评估了最具潜力诱导临床疗效的免疫治疗方法的临床前及临床证据，如免疫检查点抑制剂、CAR T细胞、肿瘤疫苗、髓系细胞重定向及溶瘤病毒疗法。尽管IMG免疫治疗已取得显著进展，但关键问题依然存在，包括最佳治疗时机与联合策略、治疗抵抗的内在机制以及克服免疫抑制微环境的策略。未来对这些治疗模式的探索，应重点关注中和TME中的可溶性免疫抑制因子、增强原位T细胞持久性及利用新型抗原靶点，这对推进目前无法治愈的这类肿瘤的治疗进展至关重要。

原文链接：

A Review of Emerging Immunotherapeutic Strategies for IDH-Mutant Glioma