Immunosenescence modulates radiation-induced anti-tumor immunity: implications for personalized immuno-oncology

Radiotherapy (RT) has evolved from a purely cytotoxic treatment into a potent immune modulator capable of inducing systemic anti-tumor responses. High-dose precision approaches such as stereotactic body radiotherapy or stereotactic radiosurgery can trigger immunogenic cell death, enhance antigen presentation, and promote tumor-specific T-cell priming. However, the magnitude and quality of these radiation-induced immune effects depend critically on the biological age of the host immune system. Immunosenescence-defined by the gradual decline and remodeling of immune competence with age-profoundly alters both innate and adaptive immunity. The aged immune landscape is characterized by reduced responsiveness, chronic low-grade inflammation, and impaired coordination between immune effector cells. In this context, RT may not elicit the same immunogenic signals observed in younger patients. Instead, aging-associated immune alterations can dampen the anti-tumor potential of radiation or shift the balance toward prolonged inflammation and immune dysregulation. These effects highlight the need to consider immune aging as a key determinant of therapeutic response. Understanding how immunosenescence modulates radiation-induced immunity is essential for developing age-informed and immune-adaptive RT strategies. Integrating biomarkers of immune aging into treatment planning could enable truly personalized immuno-oncology approaches-optimizing efficacy, minimizing toxicity, and improving outcomes in older patients with cancer.