Abstract

Hepatocellular carcinoma (HCC) is a leading cause of tumour-associated mortality worldwide, but no significant improvement in treating HCC has been reported with currently available systemic therapies. Immunotherapy represents a new frontier in tumour therapy. Therefore, the immunobiology of hepatocarcinoma has been under intensive investigation. Decoy receptor 3 (DcR3), a member of the tumour necrosis factor receptor (TNFR) superfamily, is an immune suppressor associated with tumourigenesis and cancer metastasis. However, little is known about the role of DcR3 in the immunobiology of hepatocarcinoma. In this study, we found that overexpression of DcR3 in HCC is mediated by the TGFβ3-Smad-Sp1 signalling pathway, which directly targets DcR3 promoter regions. Moreover, overexpression of DcR3 in HCC tissues is associated with tumour invasion and metastasis and significantly promotes the differentiation and secretion of Th2 and Treg cells while inhibiting the differentiation and secretion of Th1 cells. Conversely, knockdown of DcR3 expression in HCC significantly restored the immunity of CD4+ T cells. Inhibition of DcR3 expression may provide a novel immunotherapeutic approach to restoring immunity in HCC patients.

Details

Title
Role of TGFβ3-Smads-Sp1 axis in DcR3-mediated immune escape of hepatocellular carcinoma
Author
Hui-fang, Zhu 1 ; Yan-ping, Liu 2 ; Ding-li, Liu 3 ; Yi-dan, Ma 2 ; Zhi-yan, Hu 2 ; Xiao-yan, Wang 2 ; Chuan-sha Gu 1 ; Zhong, Yan 2 ; Long, Ting 2 ; He-ping, Kan 4 ; Zu-guo, Li 5 

 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China; Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China 
 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China 
 State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China 
 Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China 
 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China; Department of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China; Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China 
Pages
1-13
Publication year
2019
Publication date
Aug 2019
Publisher
Nature Publishing Group
e-ISSN
21579024
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2272720915
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.