A Promising Treatment Strategy for Lung Cancer: A Combination of Radiotherapy and Immunotherapy

SIMPLE SUMMARY: Lung cancer is a leading cause of cancer-related deaths worldwide. In the past few decades, radiotherapy has achieved outstanding technical advances and is widely used in the management of lung cancer. The anti-tumor effect of radiotherapy is mainly caused by DNA damage in cancer cells within the irradiated field. In addition, radiotherapy induces anti-tumor immune responses that are essential in cancer control. Recently, immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated protein 4, programmed cell death-1/programmed death-ligand 1, and their inhibitors, have attracted significant attention for overcoming the immunosuppressive conditions in patients with cancer. Furthermore, some studies showed that the combination of immune checkpoint inhibitors and radiotherapy appears promising. In this review, we outlined evidence about the combination of radiotherapy, including particle therapy using protons and carbon ions, with immunotherapy in lung cancer treatment. ABSTRACT: Lung cancer is a leading cause of cancer-related deaths worldwide despite advances in treatment. In the past few decades, radiotherapy has achieved outstanding technical advances and is being widely used as a definitive, prophylactic, or palliative treatment of patients with lung cancer. The anti-tumor effects of radiotherapy are considered to result in DNA damage in cancer cells. Moreover, recent evidence has demonstrated another advantage of radiotherapy: the induction of anti-tumor immune responses, which play an essential role in cancer control. In contrast, radiotherapy induces an immunosuppressive response. These conflicting reactions after radiotherapy suggest that maximizing immune response to radiotherapy by combining immunotherapy has potential to achieve more effective anti-tumor response than using each alone. Immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated protein 4, programmed cell death-1/programmed death-ligand 1, and their inhibitors, have attracted significant attention for overcoming the immunosuppressive conditions in patients with cancer. Therefore, the combination of immune checkpoint inhibitors and radiotherapy is promising. Emerging preclinical and clinical studies have demonstrated the rationale for these combination strategies. In this review, we outlined evidence suggesting that combination of radiotherapy, including particle therapy using protons and carbon ions, with immunotherapy in lung cancer treatment could be a promising treatment strategy.