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Comprehensive single-cell profiling of intratumoral T and B cells in gynecological malignancies

Identifying targets to optimize immunotherapy
PhD ceremony:Ms H.H. (Hagma) Workel
When:September 22, 2021
Supervisor:prof. dr. H.W. (Hans) Nijman
Co-supervisor:dr. M. (Marco) de Bruyn
Where:Academy building RUG
Faculty:Medical Sciences / UMCG

Our adaptive immune system is pre-eminently capable of recognizing and attacking tumor cells in a targeted manner. The studies in this thesis focus on studying these T cells and B cells in uterine and ovarian cancer in order to improve the ability of these cells to attack and destroy tumor cells. There are many different subtypes of T cells, some of which can attack tumor cells more efficiently than others. T cells expressing CD103, a subunit of an integrin, are associated with better survival in many tumors; we have shown in this thesis that this is also the case in endometrial and ovarian tumors.To determine why these CD103+ T cells are are associated with improved survival, we studied these cells at the single-cell level by (single-cell) mRNA sequencing, flow cytometry and immunohistochemistry/fluorescence a.o. In this thesis we have described the preferential location, prognostic value and transcriptional profile of CD103+ T cells in endometrial and ovarian tumors. In our analyses, we found several potential therapeutic targets to enhance the (re)activation of CD103+ T cells in tumors. In addition, we found a clear link between CD103+ T cells, expression of CXCL13 and B cells, leading to an extensive study of B cells and tertiary lymphoid structures in gynecological malignancies. The insight obtained in this thesis can hopefully contribute to improving (response) to immunotherapy. In addition, our results could aid in selecting patients with a high chance of responding to immunotherapy.