Unravelling The Tumour Immune-Biology Of Ovarian Cancer

Ovarian cancer is the fifth most lethal cancer for woman. It is a silent killer, metastasizing throughout the abdomen before causing symptoms. Consequently, over 70% of patients are diagnosed in advanced disease stages (FIGO stage III to IV). Cytoreductive surgery in combination with platinum-based chemotherapy remain the cornerstones in first-line therapy. However, risk of recurrence is high. Recently approved targeted therapies (anti-VEGF and PARP inhibitors) have improved the situation slightly for some patients, but cannot offer a cure for all patients. Five years after diagnosis, only 70% of the women will be alive. Therefore, the search for adequate treatment options is wide open.

It has been well established that the immune system is an important player in the onset and development of cancer. The immune system controls once neoplastic cells arise. Based on both the adaptive and innate immune response, tumor cells will be eliminated. In some cases, elimination is not entirely successful and an equilibrium phase is established. Neoplastic cells are still in place, but in a dormant state, side-by-side with the immune system. During this process, tumor cells can transform and consequently escape tumor control. The immune systems fails and tumor proliferation cannot be stopped. Immunosuppressive cells are attracted towards the tumor side (MDSC (myeloid derived suppressor cells), Treg (regulatory T cells), M2 macrophages, …) and will even promote tumor growth.

The aim of this thesis was to further characterize the tumor immuno-biology of ovarian cancer. Based on this information, we next aim to test different immunotherapy-based treatment combinations. Lastly, we provided a proof-of-concept study to facilitate the implementation of regular screening of the immune status of a patient in a clinical setting.