Biomarkers of immune checkpoint inhibitors in non-small cell lung cancer: beyond PD-L1

Abstract Background Immunotherapy (IT) has markedly improved the survival rate of patients with non-small cell lung cancer (NSCLC) and has introduced a new era in lung cancer treatment. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Thus, it is crucial to identify potential biomarkers suitable for screening the population that may benefit from immunotherapy. Methods Based on the current clinical trials, the aim of the present study was to review the biomarkers for immune checkpoint inhibition that may have the potential to predict the response to immunotherapy in patients with lung cancer. A non-systematic literature review was done. We searched for eligible randomized controlled trials (RCTs) from PubMed, Embase, and the Cochrane Central Register of Controlled Trials from January 2015 to January 2021. The keywords included biomarkers, immunotherapy, immune checkpoint inhibition, PD-L1 and non-small cell lung cancer. Results Of the biomarkers beyond PD-L1 that have the most evidence and predictive capacity, we would highlight; Tumor mutational burden, microsatellite instability, the LIPI index, gut microbiome and certain alterations in genes (like STK11 deletion, LKB1 kinase mutation and MDM2/4 amplification) that confer immunoresistance. Conclusions The biomarkers reviewed in this article could help us better select the IT treatment in patients with NSCLC