Biomarkers of resistance to immune checkpoint inhibitors in non-small-cell lung cancer: myth or reality?

Cancer Drug Resist. 2020 May 11;3(3):276-286. doi: 10.20517/cdr.2020.14. eCollection 2020.

Abstract

Immune checkpoint inhibitors represent a major therapeutic advance in non-small-cell lung cancer with several approved anti-programmed death-1 and anti-programmed death-L1 immunotherapies. A majority of patients however, will not respond to immune checkpoint inhibitors and display primary resistance while a subset of initially responsive patients will present secondary resistance. Thus, there is a crucial need for biomarkers to enable better prediction and diagnosis, and to overcome such resistance. Along with improvement in the understanding of immune escape, new biomarkers are being developed, including large scale proteomic, genomic and transcriptomic approaches in tumor and blood samples. We review the novel biomarkers that have been investigated in non-small-cell lung cancer and discuss how they can rationalize therapeutic strategies.

Keywords: Non-small-cell lung cancer; circulating tumor DNA; diagnostic biomarkers; immune checkpoint inhibitors; predictive biomarkers; programmed death ligand-1; resistance; tumor mutational burden.

Publication types

  • Review