The Role of Intratumor Heterogeneity in the Response of Metastatic Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors
Marcin Nicoś, Paweł Krawczyk, Nicola Crosetto, Janusz Milanowski
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.