Combining radiation therapy with immune checkpoint blockade for the treatment of small cell lung cancer

The addition of immune checkpoint blockade (ICB) therapy to standard chemotherapy has been shown to improve survival in patients with metastatic small cell lung cancer. However, the benefit is modest and there remains an unmet need for novel therapeutic approaches to enhance the effectiveness of immunotherapy in this disease, both in the early and late stages. Ionizing radiation, which is a standard treatment for small cell lung cancer, is known to trigger immunogenic cell death in tumor cells, making it an attractive partner for ICB therapies in multiple solid tumor types. However, the optimal radiation dosage and fractionation scheme, target sites for radiation, and sequencing of radiation in relation to ICB treatment are still unclear. In this review we discuss the molecular biology underlying radiation-induced tumor immunity as well as pre-clinical and clinical studies combining radiation with ICB treatments, with a focus on translational and clinical trials in small cell lung cancer.