The regulatory role of EBV-NLMP1-specific CD4 T cell immunity in N-LMP1 tumor angiogenesis

• Main Authors: Ting Yu Shi, 許庭毓
• Other Authors: K. P. Chow
• Format: Others
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/45697866503965518137

碩士 === 長庚大學 === 生物醫學研究所 === 99 === Latent membrane protein 1 (LMP1) of Epstein–Barr virus (EBV) is highly associated with the human malignancies, including nasopharyngeal carcinoma. There are multiple variants present in different geographical regions. N-LMP1 is a preferential variant in Taiwan’s NPCs. Previously, we have established an N-LMP1 tumor mouse model. By pre-immunization with irradiated N-LMP1 tumor single cells (TSC) as vaccine in the model system, we found that the vaccine activates T cell response to inhibit tumor growth. In this study, we continued to identify which T cell subset is activated, and the possible N-LMP1 T cell epitope involved in the in vivo immune regulation of tumor growth and angiogenesis. At first, we validated the anti-angiogenesis induced by TSC immunization by the H&E tissue section. The destruction of certain early neovessels was observed. Afterwards, the adoptive transfer of CD4 T cells, but not CD8 T cells, into SCID mice exhibit the inhibition of CT26/N-LMP1 tumor growth. However, since CD26/Neo tumor progression is not affected, suggesting a specific recognition of N-LMP1 by CD4 T cells. To further understand the N-LMP1-specific CD4 T cell immunity, one peptide (P186 HGPRHTDEH) was previously identified by pulsing computer-predicted peptides to dendritic cells and its stimulation of IFN-gamma production by immunized CD4 T cells. We extended the length of peptide from P186 and tested in this current study. Our in vivo and in vitro data revealed that 9 amino acids peptide may be the epitope functional in vivo to control N-LMP1 tumor growth. Moreover, the analysis of H&E stain of tumors from immunized and non-immunized, demonstrated that the P186-CD4 T cells may also inhibit angiogenesis by vessel destruction. In conclusion, we demonstated that N-LMP1 can stimulate peptide-specific CD4 T immune response to inhibit angiogenesis. Therefore, the activated LMP1-specific T cell immunity may lead to the control of EBV-associated tumor growth.