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用于预测非小细胞肺癌中检查点免疫疗法反应的新兴血液生物标志物

Emerging Blood-Based Biomarkers for Predicting Response to Checkpoint Immunotherapy in Non-Small-Cell Lung Cancer.

作者信息

Li Shumin, Zhang Chengyan, Pang Guanchao, Wang Pingli

机构信息

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Front Immunol. 2020 Oct 16;11:603157. doi: 10.3389/fimmu.2020.603157. eCollection 2020.

Abstract

Immune checkpoint inhibitors (ICIs) have brought impressive clinical benefits in a variety of malignancies over the past years, which dramatically revolutionized the cancer treatment paradigm. Monotherapy or in combination with chemotherapy of ICIs targeting programmed death 1/programmed death ligand 1 (PD-L1) has emerged as an alternative treatment for patients with advanced non-small-cell lung cancer (NSCLC). However, constrained by primary or acquired resistance, most patients obtain limited benefits from ICIs and occasionally suffer from severe immune-related adverse events. Moreover, owing to the complexity of the tumor microenvironment and the technical limitations, clinical application of PD-L1 and tumor mutation burden as biomarkers shows many deficiencies. Thus, additional predictive biomarkers are required to further advance the precision of proper patient selection, avoiding the exposure of potential non-responders to unnecessary immunotoxicity. Nowadays, an increasing number of investigations are focusing on peripheral blood as a noninvasive alternative to tissue biopsy in predicting and monitoring treatment outcomes. Herein, we summarize the emerging blood-based biomarkers that could predict the clinical response to checkpoint immunotherapy, specifically in patients with NSCLC.

摘要

在过去几年中,免疫检查点抑制剂(ICIs)在多种恶性肿瘤中带来了令人瞩目的临床益处,极大地革新了癌症治疗模式。针对程序性死亡蛋白1/程序性死亡配体1(PD-L1)的ICIs单药治疗或与化疗联合治疗,已成为晚期非小细胞肺癌(NSCLC)患者的一种替代治疗方法。然而,受原发性或获得性耐药的限制,大多数患者从ICIs中获得的益处有限,且偶尔会遭受严重的免疫相关不良事件。此外,由于肿瘤微环境的复杂性和技术局限性,将PD-L1和肿瘤突变负荷作为生物标志物的临床应用存在许多不足。因此,需要额外的预测性生物标志物来进一步提高患者选择的准确性,避免潜在无反应者暴露于不必要的免疫毒性。如今,越来越多的研究将外周血作为组织活检的非侵入性替代方法,用于预测和监测治疗结果。在此,我们总结了新兴的基于血液的生物标志物,这些生物标志物可以预测对检查点免疫治疗的临床反应,特别是在NSCLC患者中。

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