Immune checkpoint blockade for lung cancer: state of the art

As the leading cause of cancer-related death worldwide, lung cancer had historically lacked the therapeutic successes seen in other diseases. However, with the advent of targeted therapeutic strategies in non-small cell lung cancer (NSCLC) addressing molecular perturbations in EGFR, ALK, ROS1—and with recent development of second and third-generation inhibitors—there is renewed optimism in lung cancer research for this subgroup of patients. Regrettably, for the vast majority of NSCLC patients without these targetable driver aberrations, the traditional therapeutic backbone has been chemotherapy. Fortunately, an improved understanding of the tumor immune microenvironment and tumor mutanome-related neoantigen generation has revolutionized lung cancer with the promise of durable remissions in the setting of advanced disease. Immune checkpoint blockade targeting T cell inhibitory checkpoints such as CTLA-4, programmed cell death protein 1 (PD-1), and programmed death-ligand 1 (PD-L1) have shown impressive clinical responses as monotherapy in a subset of patients. The promise of biomarker-driven, personalized immunotherapeutic approaches based on each patient’s unique tumor immune microenvironment and mutanome represents a quantum leap in lung cancer therapy. Reviewed here are the recent advances in lung cancer immunotherapy, with a focus on immune checkpoint of inhibitor biomarker development and clinical efficacy data.