Understanding the checkpoint blockade in lung cancer immunotherapy

Abstract

Immunotherapies have changed the treatment strategy of some types of tumor including melanoma and, more recently, non-small-cell lung cancer (NSCLC). Immune checkpoints are crucial for the maintenance of self-tolerance and it is known that some tumors use checkpoint systems to evade antitumor immune response. The treatment of advanced NSCLC by immune-checkpoint blockade targeting the programmed cell death protein-1 (PD1/PDL1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways has led to significant clinical benefit either as monotherapy or in combination therapy. Moreover, checkpoint receptors such as lymphocyte activation gene 3 protein (LAG3), T-cell immunoglobulin mucin domain 3 (TIM3) and killer immunoglobulin-like receptors (KIRs) are also being investigated as potential immunotherapeutic targets. This review focuses on the mechanisms of action of the main checkpoint inhibitors in lung cancer and presents the most relevant results from preclinical and clinical studies on immune-based treatments.