Introduction Ovarian cancer is the 7th most common cancer globally and in Ireland. Ovarian cancer is generally detected at advanced stages. The current standard of care is failing, as there is a suboptimal response rate and a very high relapse rate along with the development of chemoresistance. Therefore, there is unmet need for new therapeutic options to tackle this disease. As more knowledge is gained on immune/tumour interactions, more and more immunotherapeutic treatments are emerging. iNKT cells are a subset of immune cells which recognise the MHC-like molecule CD1d by interacting with their TCR. Therefore, we hypothesised that epigenetic upregulation of CD1d on ovarian cancer cells might enhance the immune/tumour cell interactions.

Methods To upregulate CD1d, ovarian cancer samples were pre-exposed to several concentrations of Decitabine and a-GalCer. Then ovarian cancer cells were co-cultured with iNKT cells. To observe the ability of iNKT cells to kill Decitabine- and α-GalCer-treated ovarian cancer cells, techniques such as Immunohistochemistry, western blot and flow cytometry were used.

Results We observed that there was an increase in deregulation marker (CD107a) and granzyme B expression by iNKT cells. We also demonstrated a concentration-dependent increase in both cleaved caspase 3 and Y-H2AX expression by the ovarian cancer cells.

Conclusion/Implications Our study findings confirm the efficacy of Decitabine and a-Galcer in enhancing CD1d expression, thereby augmenting the therapeutic impact of iNKT cells on ovarian cancer. These findings pave the way for further research and developments in utilising this approach to enhance patient outcomes through precise immunotherapeutic interventions.