Background:High-grade gliomas (HGGs), particularly glioblastoma (GBM), are associated with exceptionally high mortality and inevitable recurrence. In considering novel treatment options for these devastating diseases, immunotherapies represent promising candidates. Immunotherapies have demonstrated efficacy for several advanced tumors outside the central nervous system, highlighting a potential role for these agents in treating HGGs. However, multiple challenges to immunotherapy efficacy have tempered therapeutic benefit in practice, including local and systemic immunosuppression, intratumoral heterogeneity, and various mechanisms of intrinsic and acquired resistance. In the past 30 years, diverse immunotherapeutic subclasses have been assessed for benefit against HGGs.Methods:We performed a PubMed search for randomized clinical trials performed within the last 30 years evaluating the following immunotherapy agents for high-grade gliomas: immune checkpoint inhibitors, vaccines, oncologic viruses, cytokines, and CAR T-cells. The present review offers a critical analysis of key pre-clinical and clinical trials that have shaped the immunotherapy landscape for high-grade gliomas over the past two decades.Results/Conclusions:Across the different immunotherapeutic methods and modalities explored thus far, a recurring theme emerges: while therapeutic strategies with a compelling conceptual basis are continually under development and even demonstrate a benefit in preclinical and early-phase trials, larger and later-phase trials consistently fail to produce concordantly significant outcomes. To date, no large-scale clinical trial has demonstrated a benefit of sufficient consequence to change practice. Continued critical appraisal of the strengths and pitfalls of prior investigative work, optimization of treatment development and delivery, and innovative approaches to combination therapy design will collectively be integral to future therapeutic advancement.
背景：高级别胶质瘤（HGGs），尤其是胶质母细胞瘤（GBM），具有极高的死亡率和不可避免的复发率。在探索这些毁灭性疾病的新型治疗方案时，免疫疗法展现出广阔前景。免疫疗法已在多种中枢神经系统外的晚期肿瘤治疗中显示出疗效，表明其在治疗高级别胶质瘤方面具有潜在价值。然而，免疫疗法的实际疗效受到多重挑战的制约，包括局部和全身性免疫抑制、肿瘤内异质性以及内在性和获得性耐药机制。过去三十年间，多种免疫治疗亚类已被评估用于高级别胶质瘤的治疗。 方法：我们通过PubMed检索了过去30年内评估以下免疫疗法治疗高级别胶质瘤的随机临床试验：免疫检查点抑制剂、疫苗、溶瘤病毒、细胞因子和CAR T细胞。本综述对过去二十年间塑造高级别胶质瘤免疫治疗格局的关键临床前及临床试验进行了批判性分析。 结果/结论：在迄今探索的不同免疫治疗方法与模式中，一个反复出现的主题是：尽管具有坚实理论基础的治疗策略持续发展，甚至在临床前和早期试验中显示出疗效，但更大规模的后期试验始终未能取得一致性的显著成果。迄今为止，尚无大规模临床试验证明足以改变临床实践的显著获益。持续批判性评估既往研究的优势与缺陷、优化治疗方案的开发与实施、以及创新联合疗法设计，将成为未来治疗进展不可或缺的组成部分。
肿瘤(癌症)患者之家