免疫检查点阻断疗法在治疗肺癌脑转移方面的新作用

IF 3.3 3区 医学 Q2 ONCOLOGY
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引用次数: 0

摘要

在实体器官癌症中,肺癌的脑转移(BM)发生率最高。非小细胞肺癌(NSCLC)脑转移治疗传统上采用全脑放射治疗,但立体定向放射外科已成为大多数患者的首选治疗方式。高渗透性中枢神经系统(CNS)酪氨酸激酶抑制剂也显示出对携带特定致癌驱动因子的患者具有显著的中枢神经系统活性。有新证据表明,没有癌基因驱动肿瘤的患者也能从使用免疫检查点抑制剂(ICIs)中获益。由于担心免疫检查点抑制剂的中枢神经系统穿透力和活性不足,在具有里程碑意义的试验中排除了活动性骨髓瘤患者,因此对免疫检查点抑制剂的中枢神经系统活性还没有进行深入研究。然而,鉴于中枢神经系统内存在功能性淋巴引流以及血液肿瘤对血脑屏障的破坏,研究对中枢神经系统免疫特权的观点提出了质疑。对 BM 肿瘤微环境中肿瘤和中枢神经系统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,与单纯化疗(CT)相比,使用 ICIs 的方案可改善 BM 患者的颅内反应和生存获益。两项前瞻性 2 期试验评估了 pembrolizumab 单药治疗和 atezolizumab 加 CT 治疗未经治疗的 NSCLC BM 患者,结果也显示了显著的颅内反应。本综述描述了中枢神经系统免疫细胞与肿瘤细胞之间的相互作用,讨论了目前回顾性和前瞻性研究中有关 ICI 中枢神经系统活性的证据,并对未来的研究方向进行了推测。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Emerging Role of Immune Checkpoint Blockade for the Treatment of Lung Cancer Brain Metastases

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.

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来源期刊
Clinical lung cancer
Clinical lung cancer 医学-肿瘤学
CiteScore
7.00
自引率
2.80%
发文量
159
审稿时长
24 days
期刊介绍: Clinical Lung Cancer is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of lung cancer. Clinical Lung Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of lung cancer. The main emphasis is on recent scientific developments in all areas related to lung cancer. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.
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