Published in

American Association of Immunologists, The Journal of Immunology, 9(194), p. 4577-4587, 2015

DOI: 10.4049/jimmunol.1400794

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

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

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.