Synergizing Radiotherapy and Immune Checkpoint Inhibitors in Malignant Solid Tumors: Mechanistic Insights and Translational Frontiers

Radiotherapy (RT) and immune checkpoint inhibitors (ICIs) have each revolutionized the therapeutic landscape of malignant solid tumors (STs).RT not only induces direct tumor cytotoxicity but also profoundly remodels the tumor microenvironment (TME), promoting antigen release and immune activation.ICIs-targeting cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1)-restore antitumor immunity by reversing T cell exhaustion.Accumulating evidence shows that RT enhances tumor immunogenicity and synergizes with ICIs to generate systemic immune responses through mechanisms such as the abscopal effect, immunogenic cell death (ICD), and activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway.This review integrates radiobiological and immunological principles to delineate the mechanistic basis of the synergy between RT and ICIs and to summarize recent clinical advances across multiple tumor types.We further discuss translational implications, unresolved challenges, and future strategies to optimize combinatorial regimens, improve patient selection, and advance next-generation radioimmunotherapy toward precision cancer treatment.