在实体器官癌症中，肺癌的脑转移（BM）发生率最高。传统上，全脑放射治疗已用于非小细胞肺癌 (NSCLC) BM 治疗，尽管立体定向放射外科已成为大多数患者的最佳治疗方式。高渗透性中枢神经系统 (CNS) 酪氨酸激酶抑制剂在携带特定致癌驱动因素的患者中也显示出显着的 CNS 活性。越来越多的证据表明，没有癌基因驱动的肿瘤的患者可以从免疫检查点抑制剂（ICIs）的使用中受益。由于担心 CNS 渗透和活性不足，将活动性 BM 患者排除在里程碑式试验之外，ICIs 的 CNS 活性尚未得到充分研究。然而，鉴于 CNS 内存在功能性淋巴引流以及 BM 对血脑屏障的破坏，研究对 CNS 免疫特权的想法提出了挑战。对 BM 肿瘤微环境中肿瘤和 CNS 免疫细胞之间相互作用的新认识也支持免疫疗法在 BM 治疗中的作用。此外，主要试验的事后分析表明，对于 BM 患者来说，与单独化疗 (CT) 相比，ICIs 治疗方案可改善颅内反应和生存获益。两项评估 pembrolizumab 单药治疗和 atezolizumab 加 CT 对未经治疗的 NSCLC BM 患者的前瞻性 2 期试验也显示出显着的颅内反应。这篇综述描述了中枢神经系统免疫细胞和肿瘤细胞之间的相互作用，讨论了回顾性和前瞻性研究中 ICI 中枢神经系统活性的当前证据，并推测了未来的研究方向。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Lung cancer has the highest incidence of brain metastases (BM) among solid organ cancers. Traditionally whole brain radiation therapy has been utilized for non-small-cell lung cancer (NSCLC) BM treatment, although stereotactic radiosurgery has emerged as the superior treatment modality for most patients. Highly penetrant central nervous system (CNS) tyrosine kinase inhibitors have also shown significant CNS activity in patients harboring select oncogenic drivers. There is emerging evidence that patients without oncogene-driven tumors derive benefit from the use of immune checkpoint inhibitors (ICIs). The CNS activity of ICIs have not been well studied given exclusion of patients with active BM from landmark trials, due to concerns of inadequate CNS penetration and activity. However, studies have challenged the idea of an immune-privileged CNS, given the presence of functional lymphatic drainage within the CNS and destruction of the blood brain barrier by BM. An emerging understanding of the interactions between tumor and CNS immune cells in the BM tumor microenvironment also support a role for immunotherapy in BM treatment. In addition, posthoc analyses of major trials have shown improved intracranial response and survival benefit of regimens with ICIs over chemotherapy (CT) alone for patients with BM. Two prospective phase 2 trials evaluating pembrolizumab monotherapy and atezolizumab plus CT in patients with untreated NSCLC BM also demonstrated significant intracranial responses. This review describes the interplay between CNS immune cells and tumor cells, discusses current evidence for ICI CNS activity from retrospective and prospective studies, and speculates on future directions of investigation.Copyright © 2024 Elsevier Inc. All rights reserved.