A new perspective on cancer treatment: the interaction and application prospect between ICIs and radiotherapy

Abstract The interaction between immune checkpoint inhibitors (ICIs) and radiotherapy has significantly improved the treatment outcomes for patients with cancer. ICIs activate the immune system by blocking the programmed death‐1 (PD‐1), programmed cell death‐Ligand 1(PD‐L1), and cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) signaling pathways, thereby killing tumor cells. Radiotherapy activates local and abscopal effects by killing tumor cells, inducing immunogenic death, and releasing antigens and damage‐related molecules. The combination of the two methods forms a closed‐loop process of “antigen release‐immune activation,” which significantly improves the therapeutic effect of patients with cancer. Clinical studies have shown that ICIs combined with radiotherapy can significantly improve the objective response rate (ORR) and progression‐free survival (PFS) in patients with solid tumors, such as Non‐Small Cell Lung Cancer (NSCLC) and melanoma. However, heterogeneous responses, immune‐related adverse events (irAEs), and drug resistance are still common clinical problems. Optimizing the fractionation of radiotherapy dose, timing of synchronous intervention, and biomarkers, such as tumor mutation burden, are key to improving tumor treatment efficacy. In the future, precise tumor treatment is expected to improve patient prognosis through the interaction between ICIs and radiotherapy.