Abstract
Cervical cancer remains one of the leading causes of cancer death worldwide. Immunotherapy is the most promising cancer therapeutics in recent years and has gain positive results in several cancers in the clinic. This study was aimed to investigate the roles and mechanism of IFI16 in cervical cancer immunotherapy. We observed an abnormally high expression of Programmed cell death 1 ligand 1 (PD-L1) and Interferon-inducible 16 (IFI16) in Human papillomavirus (HPV) positive cervical cancer cells compared with HPV negative cervical cancer cells. Moreover, IFI16 promotes cervical cancer development in vitro and in vivo as the oncogenic role of PD-L1. In the subsequent mechanism investigation, we found that IFI16 activated STING-TBK1-mediated immunoregulation, and subsequently activated downstream NF-kB pathway, which interacted with the proximal region of PD-L1 promoter to facilitate PD-L1 expression. In conclusion, we found that IFI16 positively regulate PD-L1 through STING-TBK1-NF-kB pathway, thus promoting cervical cancer progression. The roles of IFI16 in cervical cancer progression deserve further investigation and hold the promise of being developed as a novel immunotherapy target in the future.