Biography
Dr. Fang Zhou
Dr. Fang Zhou
University of Queensland, Australia
Title: Human papilloma virus (HPV) 16-encoded E7 onco-protein inhibits IFN-γ-mediated CTL lysis via blocking IRF-1 expression in keratinocytes
Abstract: 
Infection of HPV16 leads to induction of human cervical cancer. However, immunopathogenesis of HPV 16 is still obscure. The results of experiments aimed at determining whether or not cytotoxic T lymphocytes (CTLs) can kill endogenous antigens presented by keratinocytes (KCs) indicated that specific cytotoxic T lymphocytes could recognize and kill keratinocytes expressing ovalbumin (OVA) or SIINFEKL peptide. Interferon-gamma (IFN-γ) enhanced this CTL-mediated KC lysis via up-regulation of CTL epitope presentation on the surface of target cells. HPV 16 E7 protein as a tumour antigen affected CTL-mediated KC lysis through inhibition of IFN-γ-mediated up-regulation of SIINFEKL/H-2Kb complexes on the surface of keratinocytes. Moreover, HPV 16 E7 could inhibit IFN-γ-mediated up-regulation of IRF-1 expression, and consequent up-regulation of TAP1 transcription, so that the efficiency of SIINFEKL peptide loading on MHC class I molecules was lower than that of wild type keratinocytes. Thus, CTLs failed to efficiently recognize and kill target cells expressing E7. Effect of HPV16E7 on MHC class I antigen presentation and CTL-mediated lysis can be overcome after IRF-1 expression is restored. It can be concluded that HPV 16 E7 inhibits CD8+ T cell-mediated immune responses through blocking IRF-1 expression in host cells. These findings may help explain why HPV-infected epithelial cells can escape from immune surveillance mediated by CTLs in vivo and in vitro.
Biography: 
Dr. Fang Zhou (Joe) graduated from Ph.D (Immunology) in University of Queensland (Australia) in 2009. The research project of Dr. Joe was focused on immunopathogenesis of human papilloma virus (HPV) 16. His research data showed a new mechanism of HPV 16-encoded E7 protein as a viral product to inhibit IFN-gamma-mediated MHC class I antigen processing and CD8+ T cell-induced target cell lysis. Dr. Joe went to Thomas Jefferson University (USA) to develop immunologic research in 2010. His research was focused on molecular mechanisms of dendritic cell-mediated immune tolerance. His results indicated how tolerogenic dendritic cells modulate differentiation and development of regulatory T cells and T helper 17 cells in autoimmune disease. Dr. Joe was also awarded American Heart Association (AHA) Postdoctoral Fellowship in 2012 when he conducts research of NK cell-mediated immune responses in autoimmunity in Oklahoma Medical Research Foundation (USA). He went back to Australia in 2014 and carried out research of cancer stem cells in University of Queensland. His project was focused on how tumor stem cells escape from immune surveillance in vivo. In summary, Dr. Joe is highly trained and full of experience in immunologic research including dendritic cells,CD4+/CD8+ T cells, NK cells and cancer stem cells. He has published 16 immunological papers as the first author and corresponding author since 2009. At present, he gets a position of senior research fellow in tumor immunology and the director of research and development in Department of oncology and immunology in China. He continues to conduct research of cellular therapy and tumor vaccine development at the moment.