胶质母细胞瘤的免疫治疗综述。
A review of glioblastoma immunotherapy.
机构信息
Department of Neurosurgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Phipps 123, Baltimore, MD, 21287, USA.
Department of Neurosurgery, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
出版信息
J Neurooncol. 2021 Jan;151(1):41-53. doi: 10.1007/s11060-020-03448-1. Epub 2020 Apr 6.
INTRODUCTION
Glioblastoma is a very aggressive cancer with dismal prognosis despite standard of care including surgical resection, radiation therapy, and chemotherapy. There is interest in applying immunotherapy to glioblastoma as this modality has demonstrated remarkable improvements in the management of several solid tumors including melanoma, renal cell carcinoma, and non-small cell lung cancer. This review aims to provide an overview of the current state of glioblastoma immunotherapy.
METHODS
Literature search was performed on PubMed between 1961 and 2020.
RESULTS
Initial clinical trials of checkpoint inhibitors and vaccine therapy for glioblastoma have largely been disappointing for both primary and recurrent glioblastoma. This failure has been attributed to glioblastoma's highly immunosuppressive environment and multiple mechanisms of therapy resistance including high tumor heterogeneity, low mutational burden, systemic immunosuppression, and local immune dysfunction.
CONCLUSIONS
Current clinical trials are exploring combination therapy and novel treatment strategies beyond immune checkpoint therapies and vaccine therapy such as CAR T cells. There is also an effort to establish synergy between immunotherapy and current standard of care. Furthermore, recent advances in personalized neoantigen vaccines suggest a shift towards personalized, patient-specific GBM treatment.
简介
胶质母细胞瘤是一种非常侵袭性的癌症,尽管采用了包括手术切除、放射治疗和化学疗法在内的标准治疗方法,但其预后仍然很差。人们对将免疫疗法应用于胶质母细胞瘤产生了兴趣,因为这种疗法在管理多种实体瘤方面已经取得了显著的改善,包括黑色素瘤、肾细胞癌和非小细胞肺癌。本综述旨在概述胶质母细胞瘤免疫疗法的现状。
方法
在 1961 年至 2020 年期间,在 PubMed 上进行了文献检索。
结果
针对原发性和复发性胶质母细胞瘤,检查点抑制剂和疫苗疗法的初步临床试验结果令人失望。这种失败归因于胶质母细胞瘤高度免疫抑制的环境和多种治疗耐药机制,包括肿瘤异质性高、突变负担低、全身免疫抑制和局部免疫功能障碍。
结论
目前的临床试验正在探索联合治疗和新型治疗策略,除了免疫检查点治疗和疫苗治疗外,还包括 CAR T 细胞等。此外,还努力在免疫疗法和当前的标准治疗之间建立协同作用。此外,最近在个性化新抗原疫苗方面的进展表明,个性化、针对患者的 GBM 治疗策略正在转变。