Tumor Heterogeneity and the Immune Response in Non-Small Cell Lung Cancer: Emerging Insights and Implications for Immunotherapy

Abstract

Immunotherapy has become a critical component of treatment for non-small cell lung cancer, but many tumors develop resistance to these therapies. In this review, we summarize recent studies showing that the presence of variability within the tumor, or intratumor heterogeneity, represents an importance source of resistance to immunotherapy. We discuss different types of heterogeneity—such as those arising from mutations, gene expression differences, and changes in metabolism—and explore how these traits interact with the immune system. Finally, we propose therapeutic strategies that could be used to combat the negative impact of high tumor heterogeneity.