Investigating the effect of Platinum chemotherapy on Natural Killer Cells in the tumour microenvironment of Ovarian Cancer

Platinum chemotherapy is part of the standard of care treatment of ovarian cancer. Part of the therapeutic effect of
platinum chemotherapy has been suggested to be mediated through the immune system, but so far limited studies
have addressed this. Recent immunogenomic analysis of bulk tumours from our laboratory has shown that natural
killer (NK) cells are enriched in high-grade serous ovarian cancer (HGSOC) patients following platinum
chemotherapy treatment. In the context of cancer, NK cells are an important immune cell population for tumour
surveillance and prevention of metastasis. This study developed a co-culture assay to investigate the effect of
chemotherapy on murine HGSOC cell line sensitivity to NK cytotoxicity in vitro . We found that platinum
chemotherapy induced sensitivity to NK cell cytotoxicity, which correlated with treatment induced upregulation of
stimulatory NKG2D ligands, Mult-1 and pan-Rae-1 in one of two murine HGSOC cell lines tested. Future work
will further investigate the potential mechanisms for platinum chemotherapy induced sensitivity to NK cell
cytotoxicity in HGSOC cell lines using targeted and unbiased approaches. Furthermore, in vivo experiments will be
performed to investigate the effect of chemotherapy on NK cell infiltration and function in HGSOC syngeneic
mouse models. Understanding how chemotherapy affects tumour cell sensitivity to NK