IFI16 promotes cervical cancer progression by upregulating PD-L1 in immunomicroenvironment through STING-TBK1-NF-kB pathway
IFI16 promotes cervical cancer progression by upregulating PD-L1 in immunomicroenvironment through STING-TBK1-NF-kB pathway
复制标题
DOI：
10.1016/j.biopha.2019.109790
复制
发表时间：
2020-03-01
影响因子：
7.5
通讯作者：
Cai, Hongbing
中科院分区：
文献类型：
--
作者：
Cai, Hongning;Yan, Lin;Cai, Hongbing
子宫颈癌仍然是全球癌症死亡的主要原因之一。免疫治疗是近年来最有前途的肿瘤治疗方法，在临床上对多种肿瘤的治疗取得了积极的效果。本研究旨在探讨IFI 16在宫颈癌免疫治疗中的作用及其机制。我们观察到程序性细胞死亡1配体1（PD-L1）和干扰素诱导16（IFI 16）在人乳头瘤病毒（HPV）阳性宫颈癌细胞中的异常高表达与HPV阴性宫颈癌细胞相比。此外，IFI 16作为PD-L1的致癌作用在体外和体内促进宫颈癌的发展。在随后的机制研究中，我们发现IFI 16激活STING-TBK 1介导的免疫调节，随后激活下游NF-kB通路，与PD-L1启动子近端区域相互作用，促进PD-L1表达。总之，我们发现IFI 16通过STING-TBK 1-NF-kB通路正向调节PD-L1，从而促进宫颈癌的进展。IFI 16在宫颈癌进展中的作用值得进一步研究，并有望在未来发展为新的免疫治疗靶点。
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.