Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Cell Mol Immunol. 2024 Dec;21(12):1354-1375. doi: 10.1038/s41423-024-01226-x. Epub 2024 Oct 15.
Glioblastoma (GBM) is an aggressive and lethal type of brain tumor in human adults. The standard of care offers minimal clinical benefit, and most GBM patients experience tumor recurrence after treatment. In recent years, significant advancements have been made in the development of novel immunotherapies or other therapeutic strategies that can overcome immunotherapy resistance in many advanced cancers. However, the benefit of immune-based treatments in GBM is limited because of the unique brain immune profiles, GBM cell heterogeneity, and immunosuppressive tumor microenvironment. In this review, we present a detailed overview of current immunotherapeutic strategies and discuss the challenges and potential molecular mechanisms underlying immunotherapy resistance in GBM. Furthermore, we provide an in-depth discussion regarding the strategies that can overcome immunotherapy resistance in GBM, which will likely require combination therapies.
胶质母细胞瘤(GBM)是一种侵袭性和致命性的成人脑肿瘤。标准治疗方法提供的临床获益有限,大多数 GBM 患者在治疗后会经历肿瘤复发。近年来,在开发新型免疫疗法或其他治疗策略方面取得了重大进展,这些策略可以克服许多晚期癌症中的免疫治疗耐药性。然而,由于独特的大脑免疫特征、GBM 细胞异质性和免疫抑制性肿瘤微环境,免疫治疗在 GBM 中的获益有限。在这篇综述中,我们详细介绍了当前的免疫治疗策略,并讨论了 GBM 中免疫治疗耐药性的挑战和潜在分子机制。此外,我们还深入讨论了克服 GBM 免疫治疗耐药性的策略,这可能需要联合治疗。