title: Inhibition of A20 expression in tumor microenvironment exerts anti-tumor effect through inducing myeloid-derived suppressor cells apoptosis.
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.
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Shao
authors.affiliation: 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.
authors.forename: Xiawei
authors.initials: X
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Jiayun
authors.initials: J
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Aiping
authors.initials: A
authors.lastname: Tong
authors.affiliation: 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.
authors.forename: Xuelei
authors.initials: X
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Tinghong
authors.initials: T
authors.lastname: Ye
authors.affiliation: 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.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Deng
authors.affiliation: College of life science, Sichuan University, Chengdu 610041, China.
authors.forename: Yaxiong
authors.initials: Y
authors.lastname: Sang
authors.affiliation: 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.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Qinjie
authors.initials: Q
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Du
authors.affiliation: 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.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wen
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Fu
authors.affiliation: 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.
authors.forename: Huashan
authors.initials: H
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Shuntao
authors.initials: S
authors.lastname: Luo
authors.affiliation: 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.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology*; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000235:genetics*; D004195:Disease Models, Animal; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D007108:Immune Tolerance; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D020935:MAP Kinase Signaling System; D008546:Melanoma, Experimental; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics* / Q000276:immunology*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse