Deciphering the dendritic cell compartment in ovarian cancer to assess their potential as tumor vaccines.

Advanced stage ovarian cancer (OC) patients only have an overall 5-year survival of 20%. While targeted therapies such as PARP inhibitors have improved progression free survival, immunotherapy has so far not resulted in clear patient benefit. Importantly, the role of tumor-dendritic cells (DCs) as a key player in mounting an adaptive immune response has not been investigated yet in OC. Indeed, our lab has uncovered that vaccination with tumor-cDCs can elicit a therapeutically relevant immune response.
Therefore, in this project, we will evaluate the cDC heterogeneity in OC and the potential to use tumor-cDCs as vaccine to treat OC. More specifically, we will identify and characterize different cDC populations at the transcriptomic, proteomic and functional level in both a murine OC model and patient samples using state-of-the-art technologies. As in OC, BRCA1/2 mutations are present in 20% of the patients and determine patient outcome, their role in defining cDC function will also be studied. On top, we will investigate the impact of chemotherapy and PARP inhibitors on tumor-cDC function and assess the role of immunosuppressive cells thereon. As last, in the murine OC model, the effectiveness of the different cDC populations as OC vaccine will be assessed.
The results of this project will provide new insights into the role of cDCs in OC and will propose a novel therapeutic approach for OC that overcomes the currently witnessed barriers to effective therapeutic responses.