Radiation-induced temporal lobe injury disrupts neuro-immune crosstalk: A key driver of immune dysfunction in locally advanced nasopharyngeal carcinoma.

Abstract

Nasopharyngeal carcinoma is highly prevalent in China. Combined therapy centered on radiotherapy has significantly improved the 5-year overall survival rate of patients with locally advanced nasopharyngeal carcinoma, exceeding 80%. However, radiation temporal lobe injury remains a serious late complication. Despite advances in precision radiotherapy, its incidence is 5%-15%, considerably affecting the prognosis and quality of life of patients. Radiation temporal lobe injury is triggered by multiple mechanisms, including direct radiation-induced damage to neurons and glial cells, ischemia and hypoxia resulting from endothelial injury, and imbalanced immunoinflammatory responses dominated by M1 microglia. Importantly, radiation temporal lobe injury disrupts neuro-immune crosstalk, leading to a decrease in peripheral lymphocytes and natural killer cells, an increase in pro-inflammatory cytokines, and systemic immune suppression, thereby further increasing the risk of infection and tumor recurrence. This narrative review complies with the Scale for the Assessment of Narrative Review Articles. We systematically retrieved and organized published clinical and preclinical studies on radiation temporal lobe injury and comprehensively summarized the pathogenesis of radiation temporal lobe injury; its regulatory effects on immune function; and current prevention and treatment strategies, including precision radiotherapy optimization and drug intervention. This review aims to provide a theoretical basis for understanding the mechanisms underlying the radiation temporal lobe injury as well as prevention and treatment strategies after radical radiotherapy for nasopharyngeal carcinoma, ultimately improving the long-term quality of life of survivors of nasopharyngeal carcinoma following radical radiotherapy.