St. Vincent Hospital, 123 Summer Street, Worcester, 01608, USA.
Einstein Medical Center, 5501 Old York Rd, Philadelphia, 19141, USA.
Mol Neurobiol. 2018 Aug;55(8):7072-7078. doi: 10.1007/s12035-018-0905-3. Epub 2018 Jan 30.
Brain metastasis (BM) is one of the dreadful complications of malignancies. The prognosis after BM is extremely poor and life expectancy is meager. Currently, our treatment modalities are limited to radiotherapy and surgical resection, which also has poor outcomes and leads to various neurological deficits and affects the quality of life of patients. New treatment modality, i.e., immune checkpoint inhibitors, has brought revolution in management of melanoma, renal cancer, and non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors basically enhance the immune response of the body to fight against cancers. Immune response in the brain is highly regulated; therefore, it is challenging to use immune-modulator drugs in BM. The microenvironment of BM is rich in cytotoxic T lymphocytes and which is the target of immune checkpoint inhibitors. Few studies have shown some hope regarding use of immune checkpoint inhibitors in management of BM. It works through inhibiting immune check point gates, i.e., CTLA-4 (cytotoxic T-lymphocyte-associated protein) and PD-1/PD-L1 (programmed cell death protein-1/program death ligand-1). This article explains the basic mechanism of immune check point inhibitors, rationale behind their usage in BM, and some of the clinical studies which have shown the efficacy of immune check point inhibitors in BM.
脑转移(BM)是恶性肿瘤的一种严重并发症。BM 后的预后极差,预期寿命很短。目前,我们的治疗方法仅限于放疗和手术切除,但这些方法的效果也不佳,会导致各种神经功能缺损,并影响患者的生活质量。新的治疗方法,即免疫检查点抑制剂,已在黑色素瘤、肾癌和非小细胞肺癌(NSCLC)的治疗管理中带来了变革。免疫检查点抑制剂主要增强了机体对癌症的免疫反应。大脑中的免疫反应受到高度调节;因此,在 BM 中使用免疫调节剂药物具有挑战性。BM 的微环境富含细胞毒性 T 淋巴细胞,这是免疫检查点抑制剂的靶点。一些研究表明,免疫检查点抑制剂在 BM 管理中具有一定的应用前景。它通过抑制免疫检查点门,即 CTLA-4(细胞毒性 T 淋巴细胞相关蛋白)和 PD-1/PD-L1(程序性细胞死亡蛋白-1/程序性死亡配体-1)来发挥作用。本文解释了免疫检查点抑制剂的基本机制、在 BM 中使用它们的基本原理,以及一些临床研究表明免疫检查点抑制剂在 BM 中的疗效。