Predictive biomarkers of anti-PD-1/PD-L1 therapy in NSCLC

Abstract

Immunotherapy, especially anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) treatment has significantly improved the survival of non-small cell lung cancer (NSCLC) patients. However, the overall response rate remains unsatisfactory. Many factors affect the outcome of anti-PD-1/PD-L1 treatment, such as PD-L1 expression level, tumor-infiltrating lymphocytes (TILs), tumor mutation burden (TMB), neoantigens, and driver gene mutations. Further exploration of biomarkers would be favorable for the best selection of patients and precisely predict the efficacy of anti-PD-1/PD-L1 treatment. In this review, we summarized the latest advances in this field, and discussed the potential applications of these laboratory findings in the clinic.

Keywords: Anti-PD-1/PD-L1 therapy; Biomarkers; Efficacy prediction; Immunotherapy; NSCLC.

Fig. 1

Predictive biomarkers of anti-PD-1/PD-L1 therapy in NSCLC. First, increased PD-L1 level is an indicator of the pre-existed anti-tumor immune response which is positively correlated to response rate to anti-PD-1/PD-L1 treatment. Second, TIL is the effectors of anti-tumor immune response, which could be boosted by PD-1/PD-L1 inhibitors. Besides, TMB and neoantigens determine cancer immunogenicity which is the basis of anti-tumor response. In addition, multiple other factors such as suppressive immune cells, driver gene mutations, gut microbiota, tumor metabolites such as IDO1 also participate in anti-tumor immunity and affect the efficacy of anti-PD-1/PD-L1 therapies