Targeting activation-induced cytidine deaminase overcomes tumor evasion of immunotherapy by CTLs.
Activation-induced cytidine deaminase (AID) is an enzyme essential for the generation of Ab diversity in B cells and is considered to be a general gene mutator. In addition, AID expression was also implicated in the pathogenesis of human B cell malignancies and associated with poor prognosis. In this study, we report that small interfering RNA silencing of AID in plasmacytoma dramatically increased its susceptibility to immunotherapy by CTLs. AID silencing did not decrease the mutation frequencies of tumor Ag gene P1A. Gene-array analysis showed dramatically altered expression of a number of genes in AID-silenced plasmacytoma cells, and upregulation of CD200 was shown to be in favor of tumor eradication by CTLs. Taken together, we demonstrate a novel function of AID in tumor evasion of CTL therapy and that targeting AID should be beneficial in the immunotherapy of AID-positive tumors.
Liu
Jin-Qing
JQ
Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA.
Joshi
Pramod S
PS
Wang
Chuansong
C
El-Omrani
Hani Y
HY
Xiao
Yi
Y
Liu
Xiuping
X
Hagan
John P
JP
Liu
Chang-Gong
CG
Wu
Lai-Chu
LC
Bai
Xue-Feng
XF
D000818:Animals; D045744:Cell Line, Tumor; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018390:Gene Targeting / Q000379:methods; D016219:Immunotherapy, Adoptive / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D010954:Plasmacytoma / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D034741:RNA, Small Interfering; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
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