Nesseler Jean Philippe, Schaue Dorthe, McBride William H, Lee Mi-Heon, Kaprealian Tania, Niclou Simone P, Nickers Philippe
Department of Radiation Oncology, David Geffen School of Medicine, University of California Los Angeles, California.
NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health, Luxembourg City, Luxembourg.
Adv Radiat Oncol. 2018 Nov 20;4(2):268-282. doi: 10.1016/j.adro.2018.11.005. eCollection 2019 Apr-Jun.
Glioblastoma (GBM) remains an incurable disease despite extensive treatment with surgical resection, irradiation, and temozolomide. In line with many other forms of aggressive cancers, GBM is currently under consideration as a target for immunotherapy. However, GBM tends to be nonimmunogenic and exhibits a microenvironment with few or no effector T cells, a relatively low nonsynonymous somatic mutational load, and a low predicted neoantigen burden. GBM also exploits a multitude of immunosuppressive strategies.
A number of immunotherapeutic approaches have been tested with disappointing results. A rationale exists to combine immunotherapy and radiation therapy, which can induce an immunogenic form of cell death with T-cell activation and tumor infiltration.
Various immunotherapy agents, including immune checkpoint modulators, transforming growth factor beta receptor inhibitors, and indoleamine-2,3-dioxygenase inhibitors, have been evaluated with irradiation in preclinical GBM models, with promising results, and are being further tested in clinical trials.
This review aims to present the basic rationale behind this emerging complementary therapeutic approach in GBM, appraise the current preclinical and clinical data, and discuss the future challenges in improving the antitumor immune response.
尽管胶质母细胞瘤（GBM）经过手术切除、放疗和替莫唑胺的广泛治疗，但仍然是一种无法治愈的疾病。与许多其他侵袭性癌症形式一样，GBM目前正被视为免疫治疗的靶点。然而，GBM往往具有非免疫原性，其微环境中效应T细胞很少或没有，非同义体细胞突变负荷相对较低，预测的新抗原负担也较低。GBM还利用多种免疫抑制策略。
已经测试了多种免疫治疗方法，但结果令人失望。有理由将免疫治疗与放射治疗相结合，放射治疗可以诱导具有T细胞活化和肿瘤浸润的免疫原性细胞死亡形式。
在临床前GBM模型中，已经对包括免疫检查点调节剂、转化生长因子β受体抑制剂和吲哚胺-2,3-双加氧酶抑制剂在内的各种免疫治疗药物与放疗联合进行了评估，结果令人鼓舞，并且正在临床试验中进一步测试。
本综述旨在介绍GBM这种新兴的辅助治疗方法背后的基本原理，评估当前的临床前和临床数据，并讨论改善抗肿瘤免疫反应方面未来面临的挑战。
