Radiotherapy and Immune System Interactions Historical Perspectives and Clinical Advancements

Radiotherapy (RT) has evolved significantly since its inception from treating benign conditions to becoming a cornerstone of cancer treatment. This review examines the complex interactions between RT and the immune system, highlighting its diverse effects on various immune cell populations, and exploring emerging strategies to enhance therapeutic outcomes. We discuss lessons learned from the re‐emergence of low‐dose irradiation for non‐malignant disorders, the use of RT in managing graft‐versus‐host disease, and the importance of fractionation in modulating immune responses. This review addresses abscopal effects and their clinical implications. We emphasize the critical role of tumor‐draining lymph nodes in mediating systemic immune responses. Recent advancements, including FLASH radiotherapy and targeted approaches to preserving immune function, have been explored. By integrating historical insights with contemporary research, this review aims to guide future RT practices and optimize their immunomodulatory potential, while minimizing adverse effects. We conclude by emphasizing the need for personalized approaches, biomarker identification, and innovative combination therapies to maximize the efficacy of RT in oncology.