PDF(Pubmed)
Abstract：
Glioblastoma (GBM) is the most prevalent malignant tumor of the central nervous system. The prognosis of GBM is grim, with a median overall survival of 14.6 months and only 6.9% of patients surviving 5 years after the initial diagnosis. Despite poor outcomes, standard therapy of surgical resection, radiotherapy, chemotherapy, and tumor-treating fields has remained largely unchanged. The introduction of immune checkpoint inhibitors (ICI) has been a paradigm shift in oncology, with efficacy across a broad spectrum of cancer types. Nonetheless, investigations of ICIs in both newly diagnosed and recurrent GBM have thus far been disappointing. This lack of clinical benefit has been largely attributed to the highly immunosuppressive nature of GBM. However, immunotherapy still holds promise for the treatment of GBM, with combinatorial strategies offering hope for potentially overcoming these current limitations. In this review, we discuss the outcomes of clinical trials employing ICIs in patients with GBM. Afterward, we review ICI combination strategies and how these combinations may overcome the immunosuppressive microenvironment of GBM in the context of preclinical/clinical evidence and ongoing clinical trials.
摘要：
胶质母细胞瘤（GBM）是中枢神经系统最常见的恶性肿瘤。GBM的预后很严峻,中位总生存期为14.6个月，只有6.9%的患者在初次诊断后存活5年。尽管结果不佳，手术切除的标准疗法，放射治疗,化疗,肿瘤治疗领域基本保持不变。免疫检查点抑制剂（ICI）的引入一直是肿瘤学的范式转变，具有广泛的癌症类型的功效。尽管如此，迄今为止,新诊断和复发性GBM的ICIs调查令人失望.这种临床益处的缺乏主要归因于GBM的高度免疫抑制性质。然而,免疫疗法仍然有望治疗GBM，组合策略为潜在克服这些当前限制提供了希望。在这次审查中,我们讨论了在GBM患者中使用ICIs的临床试验的结果.之后,我们在临床前/临床证据和正在进行的临床试验的背景下,回顾了ICI组合策略以及这些组合如何克服GBM的免疫抑制微环境.
