EBV oncogene N-LMP1 induces CD4 T cell-mediated angiogenic blockade in the murine tumor model

Tzong Shoon Wu, Lian Chen Wang, Shu Chen Liu, Ting Yu Hsu, Chun Yen Lin, Gou Jin Feng, Jian Ming Chen, Hao Ping Liu, I. Che Chung, Tzu Chen Yen, Yu Sun Chang, Shuen Kuei Liao, Chen Chang, Kai Ping N. Chow

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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-Ed-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.

Original languageEnglish
Pages (from-to)4577-4587
Number of pages11
JournalJournal of Immunology
Volume194
Issue number9
DOIs
StatePublished - 1 May 2015

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