Immunological, molecular and therapeutic mechanisms in endometrial cancer

Improving outcome for patients with endometrial cancer (EC) has fueled research into immunological, molecular and therapeutic mechanisms in EC. The research in this thesis aims to further increase our understanding of the interplay between these mechanisms. In chapter 2, we questioned if selection of patients for adjuvant treatment can be improved using immunological variables. We found that a combination of disease stage, presence of lymphovascular space invasion and tumor infiltrating cytotoxic T-cells best predicts recurrence. This implies that intratumoral cytotoxic T-cells can contribute to improved patient selection. Next we examined new immunological mechanisms contributing to disease course. We found that presence of tumor infiltrating natural killer cells relates to patient survival dependent expression of human leucocyte antigen E (chapter 3). In chapter 4 we describe how mutations of Janus Kinase 1 can contribute to immune escape, an acquired trait of tumors to avoid immune destruction. Chapter 5 and 6 focus on uterine carcinosarcoma, a rare but lethal subtype of EC. We examined expression of L1CAM adhesion molecule and epithelial-mesenchymal transition, an important mechanism in cancer progression and metastasis (Chapter 5). Surprisingly, expression was not related to tumor cells with a mesenchymal phenotype but limited to cells with an epithelial phenotype. Chapter 6 describes a large retrospective cohort study on treatment in uterine carcinosarcoma and shows a survival benefit for surgery extended with a lymphadenectomy. Chapter 7 discusses the findings in this thesis in relation to the current understanding and future developments.