RFC5 enhances DNA damage response and immune escape via suppressing the cGAS-STING pathway in nasopharyngeal carcinoma.

The capacity of tumor cells to repair DNA damage is closely associated with their resistance to radiotherapy and chemotherapy. Our investigation demonstrated elevated RFC5 levels within nasopharyngeal carcinoma (NPC) cells and is involved in DNA damage repair. Mechanistic studies revealed that high RFC5 expression in NPC cells reduces the formation of micronuclei during cisplatin treatment, thereby suppressing cGAS-STING signaling activation and limiting inflammatory mediator production, which in turn promotes tumor progression. In in vivo experiments, tumors with high RFC5 expression showed reduced secretion of IFN-γ and TNF-α by CD8+T cells in the tumor immune microenvironment, along with enhanced PD-1, LAG-3, and CTLA-4 expression, leading to T cell exhaustion. Our findings suggest that RFC5 enhances the repair of cisplatin-induced DNA damage and promotes immune evasion, suggesting RFC5 is a promising therapeutic candidate for enhancing treatment outcomes in radiotherapy and chemotherapy.