Ovarian cancer is the third most common gynecological malignancy worldwide with an overall 5-year survival of only 35%. Considering this poor prognosis, novel therapies to improve outcome for ovarian cancer patients are urgently needed. One attractive option is the use of immunotherapy. Previous work has already demonstrated that immune cells infiltrating in the tumor are associated with an improved prognosis for ovarian cancer patients. Using this work as a starting point, we first analyzed how the standard-of-care for ovarian cancer, surgery combined with chemotherapy, influences the immune profile of ovarian tumors. Strikingly, we observed that mainly inactive and naive immune cells were present in the lymph node and blood of ovarian cancer patients, suggesting insufficient priming of the immune system. Nevertheless, we observed a subset of activated tumor infiltrating immune cells, although inhibited by that same tumor. Interestingly, tumor cells exposed to chemotherapy were characterized by the absence of antigen presenting complexes (major histocompatibility complex class I) on the cell surface. As antigen presentation is crucial to elicit a proper immune response, we designed a novel strategy to overcome the lack of priming in the lymph nodes to (re)activate the immune system. Within this thesis, we go on to demonstrate that targeted delivery of immune stimulating agent CD40L to the tumor- or draining lymph node micro-environment is a promising approach in this respect.
|Qualification||Doctor of Philosophy|
|Place of Publication||[Groningen]|
|Publication status||Published - 2020|