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

doi:10.3389/fonc.2020.569202

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

Front Oncol. 2020 Dec 4:10:569202. doi: 10.3389/fonc.2020.569202. eCollection 2020.

Authors

Marcin Nicoś^{1

2}, Paweł Krawczyk¹, Nicola Crosetto², Janusz Milanowski¹

Affiliations

¹ Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland.
² Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

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.

Keywords: 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.

Publication types

Review