Efficacy of PD-1 blockade therapy and T cell immunity in lung cancer patients

Abstract

Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or PD-1 ligand-1 (PD-L1) have brought paradigm shift in lung cancer treatment. The median overall survival of patients with advanced non-small cell lung cancer treated with former standard platinum doublet cytocidal therapy is less than 1 year; however, patients responding to ICIs have durable antitumor efficacy resulting in survival longer than 5 years. Lung cancer has much gene mutations, which is a characteristic of cancer caused by extrinsic factors, such as cigarette smoking. The heterogeneity underlined by genetic mutations results in the generation of resistant clones against chemotherapy and molecular targeted therapy. On the other hand, gene mutation products generate neoepitopes that are recognized as ‘non-self’ by T cell immune system. This is one of the reasons lung cancer is a good target for ICIs. However, drastic antitumor response is observed in relatively small percentage of patients. The pre-existing T cell immunity required for PD-1 inhibitor to exhibit antitumor efficacy has been elucidated.