The Role of Intratumor Heterogeneity in the Response of Metastatic Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors.

• 影响指数: 5.738
• 发表时间: 2020
• 来源期刊: Front Oncol
• DOI: 10.3389/fonc.2020.569202
• PMID: 33344229
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 医学
• 作者列表: Nicoś M,Krawczyk P,Crosetto N,Milanowski J

关键词: immunotherapy; metastatic non-small cell lung cancer (NSCLC); neoantigens; programmed-death 1 (PD-1); programmed-death ligand 1 (PD-L1); tumor heterogeneity; tumor microenvironment; tumor mutation burden

Abstract

Immune checkpoint inhibitors (ICIs) represent one of the most promising therapeutic approaches in metastatic non-small cell lung cancer (M-NSCLC). Unfortunately, approximately 50-75% of patients do not respond to this treatment modality. Intratumor heterogeneity (ITH) at the genetic and phenotypic level is considered as a major cause of anticancer therapy failure, including resistance to ICIs. Recent observations suggest that spatial heterogeneity in the composition and spatial organization of the tumor microenvironment plays a major role in the response of M-NSCLC patients to ICIs. In this mini review, we first present a brief overview of the use of ICIs in M-NSCLC. We then discuss the role of genetic and non-genetic ITH on the efficacy of ICIs in patients with M-NSCLC.