B cell landscape changes during tumour progression

Renal cell carcinoma (RCC) encompasses a group of kidney cancers that arise from the epithelial cells lining the renal tubules. Worldwide, there are over 400,000 cases of RCC each year and 70% of patients are diagnosed with clear cell RCC (ccRCC). Like many cancers, ccRCC creates an immunosuppressive tumour microenvironment (TME) to evade elimination by the immune system. Whilst the contribution of regulatory T cells (Tregs) to the immunosuppressive TME has been studied in more depth, there is a lack of understanding of the role played by regulatory B cells (Bregs) in cancer progression. We aim to use single-cell RNA-seq data performed on ccRCC tumour biopsies and matching PBMCs to identify TME-derived signals that drive Breg recruitment and suppressive activity, thus providing the opportunity to target these pathways therapeutically in vitro and in vivo. Aims: 1) to identify any changes in B cell subpopulations as the cancer progresses and what influence this has on immunosurveillance within the TME. 2) to establish patient-derived "tumouroids" co-cultured with peripheral blood Bcells/Bregs to assess the impact of the tumour on Breg phenotype/function 3) To test whether the Breg-inhibiting pathways identified in patients can be manipulated in the murine RENCA renal cancer model to trigger tumour rejection.