Non-small-cell lung cancer: Role of the immune system and potential for immunotherapy

As the leading cause of cancer death worldwide, lung cancer continues to impose a major burden on healthcare systems and cause significant challenges for clinicians and patients. Most patients present with advanced disease at the time of diagnosis and have a poor prognosis, with the vast majority surviving less than 5 years. Although new therapies have been introduced in recent years that target molecular disease drivers present in a subset of patients, there is a significant need for treatments able to improve response and extend survival while minimizing effects on quality of life. Recent evidence of clinical efficacy for immunotherapeutic approaches for lung cancer suggests that they will become the next major therapeutic advance for this disease. Non-small-cell lung cancer, which accounts for approximately 85% of lung cancer cases, has historically been considered a nonimmunogenic disease; however, as with several other malignancies, recent data show that much of this lack of immune responsiveness is functional rather than structural (i.e., possible to overcome therapeutically). This review explores the key elements of the immune system involved in non-small-cell lung cancer and briefly examines immunotherapeutic strategies in development to shift the balance of immune activity away from a tumor-induced immune-suppressive state toward an active antitumor immune response.