STING信号通路在HPV相关恶性肿瘤中的作用

Role of STING Signaling Pathway in HPV-Related Malignant Tumors

干扰素基因刺激蛋白(stimulator of interferon genes,STING)信号通路作为天然免疫通路,可以被细胞内细菌或病毒DNA片段激活,通过一系列下游信号通路促进Ⅰ型干扰素生成,是机体抗肿瘤免疫的中心组成部分。已有研究发现部分人乳头瘤病毒(human papilloma virus,HPV)阳性肿瘤组织中STING的表达上调,且高表达的STING与肿瘤患者良好预后相关,在肿瘤组织中注射STING激动剂可以观察到肿瘤组织的消退。然而也有部分研究认为,HPV存在免疫逃逸,可以在转录水平上干扰STING信号通路以及其他天然免疫途径,促进STING表观遗传学沉默和自噬降解,从而形成肿瘤局部免疫抑制微环境,促进肿瘤生长。综述STING信号通路在HPV相关恶性肿瘤中的作用,并分析STING激动剂在HPV相关恶性肿瘤治疗中的潜在应用价值。

Stimulator of interferon genes(STING)signaling pathway is a natural immune pathway,which can be activated by bacterial or viral DNA fragments in cytoplasm to promote type I interferon production through a series of downstream signaling pathways.It is a central part of the human anti-tumor immunity.Previous studies have found that STING expression was up-regulated in some human papilloma virus(HPV)-positive tumor tissues,and high expression of STING was associated with a better prognosis of tumor patients.We could observed remarkable regression of tumor when injecting STING agonists into tumor tissues.However,other studies believe that the immune escape of HPV could interfere with STING signaling pathways and other natural immune pathways at the transcriptional level,promote epigenetic silencing and autophagy degradation of STING,thus creating an immunosuppressive microenvironment of tumor and promoting tumor growth.Herein we will systematically elaborate the role of STING signaling pathway in HPV-positive malignant tumors and analyze the potential therapeutic value of STING agonists in HPV-positive tumors.