title: Targeting activation-induced cytidine deaminase overcomes tumor evasion of immunotherapy by CTLs.
abstract: 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.
authors.affiliation: Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA.
authors.forename: Jin-Qing
authors.initials: JQ
authors.lastname: Liu
authors.forename: Pramod S
authors.initials: PS
authors.lastname: Joshi
authors.forename: Chuansong
authors.initials: C
authors.lastname: Wang
authors.forename: Hani Y
authors.initials: HY
authors.lastname: El-Omrani
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.forename: Xiuping
authors.initials: X
authors.lastname: Liu
authors.forename: John P
authors.initials: JP
authors.lastname: Hagan
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.forename: Lai-Chu
authors.initials: LC
authors.lastname: Wu
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Bai
mesh_terms: 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)
chemical_list: D034741:RNA, Small Interfering; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
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