In chronic lymphocytic leukaemia (CLL), the support of the tumour microenvironment (TME) towards the leukaemic cells is crucial for disease progression and treatment resistance. As part of these supportive microenvironmental factors, leukaemia-primed fibroblasts and T cells support the malignant cells. Previous studies of our lab have shown that the protein kinase LYN within the tumour microenvironment and particularly in fibroblasts, is involved in these leukaemia-supportive effects. LYN can shape the inflammatory phenotype of fibroblasts and increases their CLL supportive capacity. Moreover, as the immunomodulative capacity of stromal cells becomes increasingly distinct, our project focusses on the impact of LYN kinase in stroma cells on their interaction with T cells. This includes the investigation of stromal LYN related changes in T cell activation, proliferation, migration and subset-composition. Furthermore, to dissect multi-cellular interactions in the TME, we want to analyse the effector function of T cells on leukaemic cells after primed by stromal cells, using established co-culture approaches.
While there are many novel cancer therapeutics targeting the immune compartment directly, for example CAR-T cells, these approaches had until now only limited success in CLL. With our research we want to investigate, if T cell function can also be modulated by targeting them not directly, but their interaction with the supportive TME.