title: EBV oncogene N-LMP1 induces CD4 T cell-mediated angiogenic blockade in the murine tumor model.
abstract: Antivascular immunity may provide long-term protection by preventing neovascularization that precedes tumor progression. Although the tumorigenesis promoted by EBV-encoded oncogene latent membrane protein 1 derived from Taiwanese nasopharyngeal carcinoma (N-LMP1) has been demonstrated, the potential of N-LMP1 for inducing immune surveillance remains elusive. In this article, we describe the immunogenicity of N-LMP1 (1510) and its induction of antivascular immunity in a transplantable tumor model in immunocompetent BALB/c mice. The immunogenicity of N-LMP1 was evaluated on the basis of tumor rejection following immunization. The impact of the immunization on the dynamics of tumor angiogenesis was assessed by temporal noninvasive dynamic contrast-enhanced magnetic resonance imaging and was further confirmed by histologic study and vascular count. Through the experiments of in vivo depletion and adoptive transfer, CD4 T cells were identified as effectors that depend on IFN-γ for tumor prevention. The response was further verified by the identification of an MHC H-2 I-E(d)-restricted peptide derived from N-LMP1 and by the immunization of mice with N-LMP1 peptide-loaded dendritic cells. These studies provide insight into N-LMP1-specific immunity in vivo, which suggests that CD4 T cells may play an important role in angiogenic surveillance against LMP1-associated cancer via tumor stroma targeting.
authors.affiliation: Exploratory Research Laboratory, Development Center for Biotechnology, New Taipei City 221, Taiwan, Republic of China;
authors.forename: Tzong-Shoon
authors.initials: TS
authors.lastname: Wu
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China; Department of Parasitology, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan, Republic of China;
authors.forename: Lian-Chen
authors.initials: LC
authors.lastname: Wang
authors.affiliation: Molecular Medical Research Center, Chang Gung University, Taoyuan 333, Taiwan, Republic of China; Institute of Systems Biology and Bioinformatics, National Central University, Taoyuan 320, Taiwan, Republic of China;
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Liu
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China;
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Hsu
authors.affiliation: Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan, Republic of China;
authors.forename: Chun-Yen
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China;
authors.forename: Gou-Jin
authors.initials: GJ
authors.lastname: Feng
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China;
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Chen
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan, Republic of China;
authors.forename: Hao-Ping
authors.initials: HP
authors.lastname: Liu
authors.affiliation: Molecular Medical Research Center, Chang Gung University, Taoyuan 333, Taiwan, Republic of China;
authors.forename: I-Che
authors.initials: IC
authors.lastname: Chung
authors.affiliation: Department of Nuclear Medicine, Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan, Republic of China;
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China; Molecular Medical Research Center, Chang Gung University, Taoyuan 333, Taiwan, Republic of China;
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Ph.D. Program for Cancer Biology and Drug Discovery, Taipei Medical University, Taipei 110, Taiwan, Republic of China;
authors.forename: Shuen-Kuei
authors.initials: SK
authors.lastname: Liao
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China; and kpc@mail.cgu.edu.tw bmcchen@ibms.sinica.edu.tw.
authors.forename: Chen
authors.initials: C
authors.lastname: Chang
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China; Department of Microbiology and Immunology, Chang Gung University, Taoyuan 333, Taiwan, Republic of China kpc@mail.cgu.edu.tw bmcchen@ibms.sinica.edu.tw.
authors.forename: Kai-Ping N
authors.initials: KP
authors.lastname: Chow
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D009389:Neovascularization, Pathologic / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D014763:Viral Matrix Proteins