IFI16/204 Promotes Dendritic Cell Activation and Anti-Hepatocellular Carcinoma Efficacy via the STING-TBK1-IRF3 Signalling Pathway

  • Immunology. 2026 May 17. doi: 10.1111/imm.70152.
Long Zhang  1  2  3 ,  Wenjing He  1  2  3 ,  Hanyuan Zhang  1  2  3 ,  Xuzhi Zhang  1  2  3 ,  Hanyu Wang  1  2  3 ,  Shuai Wang  1  2  3 ,  Xinyi Li  4 ,  Yifang Gao  1  2  3 ,  Yi Ma  1  2  3
Affiliations
  • 1. Department of Organ Transplantation, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 2. Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 3. Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 4. School of Nursing, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
PMID: 42144282 DOI: 10.1111/imm.70152
Abstract

IFI16 (the murine homologue is IFI204) is an intracellular double-stranded DNA (dsDNA) pattern recognition receptor (PRR) that plays a crucial role in bridging innate and adaptive immunity. However, its function in dendritic cell (DC) activation and anti-hepatocellular carcinoma (HCC) efficacy remains poorly characterised. This study demonstrates that IFI16 promotes DC maturation, functional activation and antitumor immunity. This effect occurs through activation of the STING-TBK1-IRF3 signalling pathway. Our findings establish IFI16 as a key molecule enabling DCs to sense dsDNA and initiate antitumor responses. Consequently, targeting IFI16 and its downstream STING-TBK1-IRF3 signalling pathway represents a potential therapeutic strategy for hepatocellular carcinoma.

Keywords
IFI16; IFI204; STING; hepatocellular carcinoma; pattern recognition receptor; tumour immunology.
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