Background: Glioblastoma (GBM) is the most common primary malignant brain tumor, with fewer than 5% of patients surviving five years after diagnosis. The introduction of immune checkpoint inhibitors (ICIs), followed by chimeric antigen receptor (CAR) T-cell therapy, marked major advancements in oncology. Despite demonstrating efficacy in other blood and solid cancers, these therapies have yielded limited success in clinical trials for both newly diagnosed and recurrent GBM. A deeper understanding of GBM’s resistance to immunotherapy is essential for enhancing treatment responses and translating results seen in other cancer models. Objectives: In this review, we examine clinical trial outcomes involving ICIs and CAR-T for GBM patients and explore the evasive mechanisms of GBM and the tumor microenvironment. Findings and Discussion: Multiple clinical trials investigating ICIs in GBM have shown poor outcomes, with no significant improvement in progression-free survival (PFS) or overall survival (OS). Results from smaller case studies with CAR-T therapy have warranted further investigation. However, no large-scale trials or robust studies have yet established these immunotherapeutic approaches as definitive treatment strategies. Future research should shift focus from addressing the scarcity of functional T cells to exploiting the abundant myeloid-derived cells within the tumor microenvironment. Conclusions: Translating these therapies into effective treatments for glioblastoma in humans remains a significant challenge. The highly immunosuppressive nature of GBM and its tumor microenvironment continue to hinder the success of these innovative immunotherapeutic approaches. Targeting the myeloid-derived compartment may lead to more robust and sustained immune responses.
背景：胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤，确诊后患者五年生存率不足5%。免疫检查点抑制剂（ICIs）的引入及随后的嵌合抗原受体（CAR）T细胞疗法，标志着肿瘤治疗领域的重大进展。尽管这些疗法在其他血液肿瘤和实体瘤中显示出疗效，但在新诊断及复发性GBM的临床试验中收效甚微。深入理解GBM对免疫治疗的抵抗机制，对于提升治疗反应及转化其他癌症模型的成功经验至关重要。 目的：本文综述了涉及GBM患者的ICIs与CAR-T临床试验结果，并探讨GBM及其肿瘤微环境的免疫逃逸机制。 发现与讨论：多项针对GBM的ICIs临床试验结果均不理想，无进展生存期（PFS）和总生存期（OS）均未获得显著改善。小规模CAR-T疗法的个案研究结果值得进一步探索，但目前尚无大规模试验或有力研究能确立这些免疫疗法作为确定性治疗策略。未来研究应将重点从解决功能性T细胞不足转向利用肿瘤微环境中丰富的髓系来源细胞。 结论：将这些疗法转化为对人类胶质母细胞瘤的有效治疗仍面临重大挑战。GBM及其肿瘤微环境的高度免疫抑制特性持续阻碍着这些创新免疫治疗方法的成功。靶向髓系细胞区室可能引发更强大且持久的免疫应答。
Immune Resistance in Glioblastoma: Understanding the Barriers to ICI and CAR-T Cell Therapy
肿瘤(癌症)患者之家