Ser Merve Hazal, Webb Mason J, Sener Ugur, Campian Jian L
Department of Neurology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.
Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
J Immunother Precis Oncol. 2024 May 2;7(2):97-110. doi: 10.36401/JIPO-23-34. eCollection 2024 May.
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.
胶质母细胞瘤（GBM）是中枢神经系统最常见的恶性肿瘤。GBM的预后严峻，中位总生存期为14.6个月，初诊后仅6.9%的患者能存活5年。尽管预后不佳，但手术切除、放疗、化疗和肿瘤电场治疗等标准治疗方法在很大程度上仍未改变。免疫检查点抑制剂（ICI）的引入是肿瘤学领域的一次范式转变，对多种癌症类型都有效。然而，迄今为止，在新诊断和复发性GBM中对ICI的研究结果令人失望。临床益处的缺乏很大程度上归因于GBM高度免疫抑制的特性。然而，免疫疗法对GBM的治疗仍有希望，联合策略有望潜在地克服当前这些局限性。在本综述中，我们讨论了在GBM患者中使用ICI的临床试验结果。之后，我们根据临床前/临床证据和正在进行的临床试验，综述ICI联合策略以及这些联合策略如何克服GBM免疫抑制微环境。
