Radiotherapy in Lung Cancer: Ally or Foe of Immunotherapy?

Abstract

Radiotherapy is the most common local treatment for lung cancer. The spectrum of its use ranges from the treatment of early-stage tumors in patients who are not candidates for surgery to the treatment of advanced, unresectable tumors and, very frequently, of metastatic lesions. With great interest, radiotherapy has also been currently cited as a source of neoantigens, stimulating the immune system and enhancing the effect of immunomodulatory drugs. However, the side effects of irradiation on the lung parenchyma and on the immune system can turn it into a hidden foe, impairing patients’ quality of life and survival. Pneumonitis and immunosuppression are two of the side effects of radiotherapy that best exemplify this hidden damage. Studies have shown decreased survival in patients who develop radiation pneumonitis or have a large volume of immune tissue irradiated. Irradiating less lung tissue will reduce damage to lung function and loss of immune cells. However, this alone is not sufficient for dose protection in lymphoid tissue, given the circulation of lymphoid cells in the great vessels and heart and their production in thoracic vertebral bone marrow. Identifying the optimal total dose and the most appropriate daily dose to reduce damage and boost the immune system is the target of our investigations. Although we still do not have an optimal algorithm for dose, fraction, and cost-effectiveness for radiation doses delivered to healthy tissues, we know which path to take.