Radiation-Induced Immunogenic Cell Death for Cancer Radioimmunotherapy

In cancer treatment, traditional radiotherapy (RT) is routinely conducted in local tumors and limited by radioresistance, while recently emerged immunotherapy is confronted with low response rate, high cost, and cytokine release syndrome. Logically, the combination of the two therapeutic modalities into radioimmunotherapy is promising to complement with each other for systemic elimination of cancer cells with high specificity, efficiency, and safety. Especially, RT-induced immunogenic cell death (ICD) plays an imperative role in radioimmunotherapy to evoke systemic immune response against cancer, including elevating the immunity of tumor antigens, recruiting and activating antigen-presenting cells, and priming cytotoxic T lymphocytes for tumoral infiltration and cancer cell eradication. This review first retrospects the origin and concept of ICD, summarizes the major damage-associated molecular patterns and signaling pathways, and highlights the characteristics of RT-induced ICD. Subsequently, therapeutic strategies enhancing RT-induced ICD for radioimmunotherapy are reviewed from the perspectives of enhancing RT itself, combination with other treatments, and stimulating the holistic immune system. On the basis of these published research and underlying mechanism, this work attempts to forecast possible directions for RT-induced ICD enhancement to promote clinical applications.