Combining radiotherapy with CAR-T cell therapy for solid tumors: Challenges, mechanisms, and future directions

Chimeric antigen receptor (CAR)-T cell therapy has achieved significant success in treating hematological malignancies. However, compared to its efficacy against hematologic cancers, the application of CAR-T cell therapy for solid tumors still faces several challenges. Radiotherapy, an important component in the treatment of solid tumors, has recently attracted widespread attention because of its immunomodulatory effects. Combined radiotherapy may overcome the limitations of CAR-T cell therapy for solid tumors. This review discusses the theoretical foundations of combined radiation therapy and CAR-T cell therapy, along with preclinical and clinical research progress. Additionally, this study provides an innovative exploration of key factors to be considered when combining these two therapies. These factors include radiation dose, mode, radiation type, and timing and scheduling of the combined treatment. This review offers new perspectives on future research directions and highlights critical issues that remain to be addressed.