PhD ceremony Ms. M.C.A. Wouters: The immune environment in ovarian cancer

Each year, approximately 1000 women in the Netherlands are diagnosed with ovarian cancer. The disease has an extremely poor prognosis and new treatment strategies are urgently needed. It is known that the immune system influences the survival of these patients and immunotherapy might therefore be a new effective form of treatment. Immunotherapy is a general term for strategies directed at inducing an immune reaction and/or improving the already existing immune response in order to support the body to eliminate the cancer.

In this thesis, we analysed the immune response against ovarian cancer in order to find new targets for immunotherapy. We found that a younger, less-differentiated subtype of T-cells is highly predictive for a better prognosis. Further, suppressive immune cell populations (subset of macrophages) present in the tumour environment correlated with worse prognosis. This suggests that for the treatment of ovarian cancer, combination strategies will be necessary that both stimulate the anti-tumour response and additionally inhibit the suppressive mechanisms. Finally, there is an urgent need for markers that could define patients that might benefit from such strategies. In this thesis, we provide evidence for the use of PD-L1 for selection of patients most likely to benefit from immunotherapy. In addition, we show that certain claudin proteins are overexpressed in ovarian cancer and might therefore provide an excellent target for therapy. Taken together, studies described in this thesis will further improve the development of immunotherapies and selection criteria for ovarian cancer patients most likely to benefit from these approaches.

Dissertation: http://hdl.handle.net/11370/b3370a61-8249-4f32-8dcc-3ac0d84b93b8