The advent of immune checkpoint inhibitor therapies have revolutionized the treatment of lung cancer, however, many patients do not derive benefit from checkpoint blockade, highlighting a need for alternative approaches to modulate the immune response. Federico Cappuzzo, MD, PhD, Istituto Nazionale Tumori, Rome, Italy, addresses resistance to immune checkpoint blockade therapies in patients with non-small cell lung cancer (NSCLC), touching on the mechanisms leading to the development of either primary or secondary resistance. This interview took place during the virtual European Lung Cancer Congress 2022.