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-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.

Nasopharyngeal carcinoma ecology theory: cancer as multidimensional spatiotemporal “unity of ecology and evolution” pathological ecosystem

“…We must be aware that the research on immune cells of NPC has a long history. Since the 1970s, lots of efforts have been made to evaluate the expression levels of immune cells and their prognostic values (155)(156)(157)(158)(159)(160) by immunohistological analysis, flow cytometry or other experimental methods in NPC, as well as the related molecular regulations (161)(162)(163)(164)(165). With the advancement of technologies such as single-cell transcriptomic analysis, the complex heterogeneity and dynamic landscape changes of tumor immune microenvironment (TIME) in NPC has been well described (32)(33)(34)(35)(36).…”

Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer

“…The majority (95%) of histopathological types of head and neck cancer is squamous cell carcinoma (HNSCC) (2). Virus-related nasopharyngeal carcinoma will be included in this review because of its immunogenicity and encouraging trial outcomes (3,4). The tumorigenesis can separate head and neck cancers into virus-related (Epstein-Barr virus-related nasopharyngeal carcinoma (NPC) and human papillomavirus (HPV)-positive oropharyngeal HNSCC) cancer and non-viral (HPV-negative) HNSCC, the latter being related to smoking, alcohol, and betel quid consumption in etiology.…”