Glioblastoma (GBM) is a highly malignant and aggressive primary brain tumor mostly prevalent in adults and is associated with a very poor prognosis. Moreover, only a few effective treatment regimens are available due to their rapid invasion of the brain parenchyma and resistance to conventional therapy. However, the fast development of cancer immunotherapy and the remarkable survival benefit from immunotherapy in several extracranial tumor types have recently paved the way for numerous interventional studies involving GBM patients. The recent success of checkpoint blockade therapy, targeting immunoinhibitory proteins such as programmed cell death protein-1 and/or cytotoxic T lymphocyte-associated antigen-4, has initiated a paradigm shift in clinical and preclinical investigations, and the use of immunotherapy for solid tumors, which would be a potential breakthrough in the field of drug therapy for the GBM treatment. However clinical trial showed limited benefits for GBM patients. The main reason is drug resistance. This review summarizes the clinical research progress of immune checkpoint molecules and inhibitors, introduces the current research status of immune checkpoint inhibitors in the field of GBM, analyzes the molecular resistance mechanism of checkpoint blockade therapy, proposes corresponding re-sensitive strategies, and describes a reference for the design and development of subsequent clinical studies on immunotherapy for GBM.

胶质母细胞瘤（GBM）是一种高度恶性和侵略性的原发性脑肿瘤，多见于成人，预后很差。而且，由于它们对脑实质的快速侵袭和对常规疗法的抵抗力，因此仅可获得几种有效的治疗方案。然而，癌症免疫疗法的快速发展以及在几种颅外肿瘤类型中免疫疗法的显着生存获益最近为涉及GBM患者的众多干预性研究铺平了道路。针对免疫抑制蛋白（例如程序性细胞死亡蛋白-1和/或细胞毒性T淋巴细胞相关抗原4）的检查点封锁疗法的最新成功，已引发临床和临床前研究的范式转变，以及免疫疗法在实体瘤治疗中的应用，这将是GBM治疗药物治疗领域的潜在突破。但是，临床试验显示，GBM患者获益有限。主要原因是耐药性。综述了免疫检查点分子及其抑制剂的临床研究进展，介绍了免疫检查点抑制剂在GBM领域的研究现状，分析了检查点阻断疗法的分子耐药机制，提出了相应的敏感性策略，并提供了参考。用于GBM免疫疗法后续临床研究的设计和开发。