Non-small cell lung cancer in the era of immunotherapy

Immunotherapy for non-small cell lung cancer (NSCLC) has revolutionized treatment for those with advanced disease, and recent data have emerged providing evidence for its benefits in earlier stages of the disease. Several pivotal clinical trials provide compelling data that adaptive immune cells may be highly effective and possibly even curative for NSCLC. Immune checkpoint inhibitors (ICIs) can unleash highly reactive memory immune responses to tumor antigens with durable effects against advanced or recurrent disease. Despite these encouraging results, many critical questions remain in the field including, for example, how to identify the subsets of NSCLC patients who most benefit from ICI treatment, and how ICI efficacy might be enhanced by utilizing combinations or sequencing of agents. A deeper understanding of biological mechanisms involved in lung cancer offers a unique opportunity to further explore the interaction between the adaptive immune landscape and NSCLC. Given the high incidence of lung cancer in Veterans and many Veterans being treated with immunotherapy for this disease, it is timely to have their adequate representation in future clinical trials. New clinical trials focused on Veterans can assist in exploring ways to mitigate resistant mechanisms as well as to investigate predictive and prognostic biomarkers for response to ICIs and other treatments. This paper will review current data and indications for immunotherapy in NSCLC, introduce new areas of research within immunotherapy, and discuss its applicability to the Veteran population.