Genotypic and phenotypic determinants of immunity across gynecological malignancies
Immunotherapy is emerging as oncological treatment strategy. To enhance immunotherapy efficacy in gynecological cancers, the studies in this dissertation aimed to improve understanding of immunological aspects in gynecological cancers. To this end, initiation of the anti-tumor response and determinants of this response were analyzed at both a genetic and protein level. Moreover, a novel manner to study cancer immunotherapy in the preclinical setting is proposed. Expression of STING, a protein with an important role in the initiation of immunity against cancer cells with DNA damage or infection, appeared to be decreased in patients with cervical cancer. This decrease coincided with worse prognosis. Therapeutic intervention to activate STING may be beneficial in the treatment of cervical cancer. Furthermore, patients with specific genetic variations in the STING-encoding gene also had worse prognoses. Genetic screening to determine prognosis could be considered. The CD8+ T cell is an important type of immune cell in the elimination of cancer cells. Various markers such as CD103, PD-1 and CD39 enable identification of anti-cancer reactive CD8+ T cells. In this dissertation, transcriptional profiles were obtained for these cells. Notably, CD103 marked cells that secreted the chemokine CXCL13, thereby linking T cells, B cells and formation of tertiary lymphoid structures. Induced pluripotent stem cells, established from the urine of cancer patients, showed potential to create novel preclinical models for immunotherapy in (gynecological) cancer.