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免疫检查点阻断疗法治疗胶质母细胞瘤的研究进展。

Treatment Progress of Immune Checkpoint Blockade Therapy for Glioblastoma.

机构信息

Medical Oncology Department, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.

Medical Oncology Department, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China.

出版信息

Front Immunol. 2020 Nov 30;11:592612. doi: 10.3389/fimmu.2020.592612. eCollection 2020.

Abstract

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.

摘要

胶质母细胞瘤(GBM)是一种高度恶性和侵袭性的原发性脑肿瘤,主要发生在成年人中,预后极差。此外,由于其快速侵袭脑实质和对常规治疗的耐药性,仅有少数有效的治疗方案可用。然而,癌症免疫疗法的快速发展以及免疫疗法在几种颅外肿瘤类型中带来的显著生存获益,最近为涉及 GBM 患者的众多介入性研究铺平了道路。最近,针对免疫抑制蛋白(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)的检查点阻断疗法的成功,引发了临床和临床前研究的范式转变,免疫疗法在实体瘤中的应用将是 GBM 治疗领域药物治疗的潜在突破。然而,临床试验显示免疫检查点分子和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,提出了相应的再敏感策略,为后续 GBM 免疫治疗的设计和开发提供了参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93d6/7734213/dbcc81246385/fimmu-11-592612-g001.jpg

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