Inhibition of A20 expression in tumor microenvironment exerts anti-tumor effect through inducing myeloid-derived suppressor cells apoptosis
Authors: Huashan Shi
Xiawei Wei
Xuelei Ma
Xiang Gao
Wei Du
Jiayun Yu
Yuquan Wei
Hongxin Deng
Aiping Tong
Min Luo
Ping Fu
Tinghong Ye
Yu Ma
Jing Du
Qinjie Wu
Yi Wen
Shuntao Luo
Yaxiong Sang
Bin Shao
Xiao Liang
Journal: Scientific Reports (2015)
Discipline: Multidisciplinary
Keywords: Myeloid-derived suppressor cells (MDSCs); A20; tumor microenvironment; small interfering RNA (si-A20); tumor growth
Affiliations: Division of Nephrology of Department of Internal Medicine and Lab of Aging Research, State Key Laboratory of Biotherapy &Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China., College of life science, Sichuan University, Chengdu 610041, China.

Abstract:  Myeloid-derived suppressor cells (MDSCs) are known to play important roles in the development of immunosuppressive tumor microenvironment. A20 is a zinc-finger protein which could negatively regulate apoptosis in several cell types. However, the role of A20 in tumor microenvironment remains largely unknown. In this study, we found that A20 was over-expressed in MDSCs. The treatment of tumor-bearing mice with small interfering RNA targeting A20 (si-A20) inhibited the growth of tumors. The infiltration of MDSCs was dramatically reduced after si-A20 treatment, as compared to control groups, whereas the numbers of dendritic cells and macrophages were not affected. Also, injection of si-A20 improved T cell mediated tumor-specific immune response. Depletion of MDSCs with anti-Gr1 antibody showed similar antitumor effect and improved T cell response. TNF-α was highly expressed after si-A20 injection. Furthermore, si-A20 induced apoptosis of MDSCs in the presence of TNF-α both in vivo and in vitro. Cleaved Caspase-3 and Caspase-8 were elevated with the activation of JNK pathway after the induction of MDSC apoptosis by si-A20. Thus, our findings suggested that knockdown of A20 in tumor site inhibited tumor growth at least through inducing the apoptosis of MDSCs. A20 might be a potential target in anticancer therapy. 

Retracted: No

PubPeer comments:
 Figure 3B * Red boxes: In the top row, the  si-SCR and  si-A20 panels appear to look very similar, while the gated percentages are different. Could the authors clarify, please? ![file] , 
 #1 Dear Dr. Elisabeth M Bik, Thank you very much for pointing out the mistake of Figure 3B in our published work. We have carefully investigated our raw data and found that this error was inadvertently made during the preparation of the manuscript. We will contact the journal editorial office as soon as possible to correct the error. Xiawei Wei , 
 #1 CORRECTION We have carefully investigated our raw data and found that this error was inadvertently made during the preparation of the manuscript. In the originally published Figure 3b, the figure of si-SCR was inadvertently duplicated with si-A20. The new images have been replaced as follow. We sincerely apologize for this oversight. Bin Shao ![file] , 
 Dear Dr. Shao and Dr. Wei, It has been about two years, and there does not seem to be a correction issued for this paper yet. Would you have any updates to share here, please? ,