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Updated: Jan 12, 2026

Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
RFC5 enhances DNA damage response and immune escape via suppressing the cGAS-STING pathway in nasopharyngeal
Yumo Han1, Mengyu Miao2, Ying Shan1
1Institute of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Xisi Road 20, Nantong 226001, China; Medical School, Nantong University, Qixiu Road 19, Nantong 226001, China; Department of Otorhinolaryngology Head and Neck surgery, Affiliated Hospital of Nantong University, Xisi Road 20, Nantong 226001, China.
Abstract:
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.
Insights
High RFC5 expression in nasopharyngeal carcinoma (NPC) promotes DNA repair and immune evasion, hindering chemotherapy and radiotherapy effectiveness. Targeting RFC5 could improve cancer treatment outcomes.
Area of Science:
- Oncology
- Cancer Biology
- Immunology
Background:
- Tumor cell DNA repair capacity correlates with resistance to radio/chemotherapy.
- Nasopharyngeal carcinoma (NPC) exhibits resistance to conventional cancer treatments.
Purpose of the Study:
- To investigate the role of RFC5 in DNA damage repair and immune evasion in NPC.
- To explore RFC5 as a potential therapeutic target for enhancing cancer treatment.
Main Methods:
- Assessed RFC5 expression in NPC cells.
- Conducted mechanistic studies on DNA damage repair and cGAS-STING signaling.
- Performed in vivo experiments to evaluate immune microenvironment changes and T cell exhaustion.
Main Results:
- Elevated RFC5 expression in NPC cells enhances DNA repair, reducing cisplatin-induced DNA damage and micronuclei formation.
- High RFC5 suppresses cGAS-STING signaling, inflammatory mediator production, and promotes tumor progression.
- RFC5 overexpression leads to reduced IFN-γ and TNF-α secretion, increased PD-1, LAG-3, CTLA-4 expression, and T cell exhaustion in vivo.
Conclusions:
- RFC5 facilitates cisplatin-induced DNA damage repair and promotes immune evasion in NPC.
- RFC5 is a potential therapeutic target for overcoming treatment resistance and enhancing outcomes in radiotherapy and chemotherapy.
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