E-Poster Presentation 34th Lorne Cancer Conference 2022

Targeting MYCN to enhance anti-tumour immunity in Ovarian Cancer (#326)

Gowri Irgam 1 , Rui Chen 1 , Andrew Wilkinson 1 , Chintan Bhavsar 1 , Raymond steptoe 2 , Sherry Wu 1
  1. School of Biomedical sciences, The University of Queensland, Brisbane, QLD, Australia
  2. The University of Queensland Diamantia Institute, The University of Queensland, Brisbane, QLD, Australia

Although a high percentage of ovarian tumours initially respond to standard chemotherapy, recurrence is a major clinical problem. While immunotherapy represents an attractive means to decrease disease recurrence, emerging data shows limited efficacy of immune checkpoint inhibitors in high grade serous ovarian cancer. This low response rate stems from the low infiltrating cytotoxic T-cells in ovarian tumours. It is well reported that overexpression of MYCN proto-oncogene is associated with low immune cell infiltration in human ovarian tumours. This project aims to investigate the role of MYCN in regulating T-cell trafficking and function in ovarian tumours. Hence, we hypothesize that MYCN knockdown can increase T-cell penetration, function in ovarian tumours and enhance the efficacy of current immune therapy. Downregulation of MYCN expression, using a combined shRNA and siRNA approach in orthotopic immune-competent mouse ovarian cancer model reduced tumour burden and increased overall survival of mice either alone or in combination with chemotherapy. MYCN downregulation in tumours resulted in a significant decrease in immunosuppressive macrophages and an increase in CD4 memory T-cells, CD8 memory T-cells in tumours. Overall, our data suggest that MYCN silencing can shift the dynamics of the tumour immune microenvironment from immunosuppressive to immune-stimulatory state.