Department of Neurology and Brain Tumor Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
Oncol Res Treat. 2016;39(6):326-34. doi: 10.1159/000446338. Epub 2016 May 25.
The brain has long been considered an immune-privileged site precluding potent immune responses. Nevertheless, because of the failure of conventional anti-cancer treatments to achieve sustained control of intracranial neoplasms, immunotherapy has been considered as a promising strategy for decades. However, several efforts aimed at exploiting the immune system as a therapeutic weapon were largely unsuccessful. The situation only changed with the introduction of the checkpoint inhibitors, which target immune cell receptors that interfere with the activation of immune effector cells. Following the observation of striking effects of drugs that target CTLA-4 or PD-1 against melanoma and other tumor entities, it was recognized that these drugs may also be active against metastatic tumor lesions in the brain. Their therapeutic activity against primary brain tumors is currently being investigated within clinical trials. In parallel, other immunotherapeutics such as peptide vaccines are at an advanced stage of clinical development. Further immunotherapeutic strategies currently under investigation comprise adoptive immune cell transfer as well as inhibitors of metabolic pathways involved in the local immunosuppression frequently found in brain tumors. Thus, the ongoing implementation of immunotherapeutic concepts into clinical routine may represent a powerful addition to the therapeutic arsenal against various brain tumors.
大脑长期以来被认为是一个免疫特权部位，阻止了强烈的免疫反应。然而，由于传统的抗癌治疗未能持续控制颅内肿瘤，免疫疗法几十年来一直被认为是一种有前途的策略。然而，旨在利用免疫系统作为治疗武器的几项努力在很大程度上都没有成功。这种情况只有在引入检查点抑制剂后才发生改变，这些抑制剂针对的是干扰免疫效应细胞激活的免疫细胞受体。在观察到针对黑色素瘤和其他肿瘤实体的靶向 CTLA-4 或 PD-1 的药物具有显著疗效后，人们认识到这些药物也可能对大脑中的转移性肿瘤病变有效。目前正在临床试验中研究这些药物对原发性脑肿瘤的治疗活性。与此同时，其他免疫疗法药物，如肽疫苗，也处于临床开发的后期阶段。目前正在研究的其他免疫治疗策略包括过继免疫细胞转移以及代谢途径抑制剂，这些抑制剂通常存在于脑肿瘤的局部免疫抑制中。因此，免疫治疗概念正在被纳入临床常规，这可能是对抗各种脑肿瘤的治疗武器库的有力补充。
