Targeting Immune Checkpoints in Lung Cancer: Current Landscape and Future Prospects

Lung cancer is the most prevalent and deadly cancer worldwide. Immune checkpoint therapy, which targets regulatory pathways in T cells to boost anti-tumor immune response, has revolutionized lung cancer treatment paradigms. Inhibitors of the most established immune checkpoints such as programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) have been approved by the US Food and Drug Administration in the management of lung cancer. Despite the pronounced survival benefits that have been seen with immune checkpoint inhibitors, not all lung cancer patients respond to single-agent immunotherapy due to the complexity of the immune microenvironment and tumor resistance. Alternative immune checkpoints beyond PD-1/PD-L1 must be sought so that more patients can benefit from immune checkpoint therapy. Additionally, novel combination strategies of immunotherapy and conventional treatments (e.g., chemotherapy, radiotherapy, and targeted therapy) have shown promise in some clinical trials. Meanwhile, identification of predictive biomarkers is pivotal in selecting eligible patients for immunotherapy and to guide individualized clinical decision-making. The future of immune checkpoint therapy in lung cancer is not devoid of challenges, and more prospective clinical studies are awaited to translate our understanding from bench to bedside.