Immunotherapy combined with radiotherapy for advanced non-small cell lung cancer: Current status and challenge (Review)

Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the treatment landscape for advanced non-small cell lung cancer (NSCLC) in previous years. However, not all patients achieve a satisfactory objective response and long-term benefits, leading to growing interest in combining immunotherapy with radiotherapy (RT) to enhance therapeutic outcomes. The present review explored the rationale, efficacy and safety of combining RT with immunotherapy in advanced NSCLC. RT can potentiate immune responses through various mechanisms, such as immunogenic cell death and modification of the tumor microenvironment. The addition of RT to immunotherapy has notable synergistic antitumor effects to improve systemic control as RT can induce diverse immunomodulatory effects. The present review assessed the efficacy and safety of combining ICIs with RT and examined the optimal timing, dose and fraction strategies of RT for enhancing immune activation while minimizing toxicity. Additionally, the potential of RT to overcome primary and acquired resistance to immunotherapy was discussed. Despite encouraging findings, challenges such as optimal patient selection and biomarkers, treatment-related toxicity and precise timing of interventions remain unresolved. The present review aimed to provide a comprehensive analysis of current evidence, as well as the key considerations for integrating RT and immunotherapy into clinical practice.