Roland Geisberger, PhD
IIIrd Medical Department
University Clinics Salzburg
Leukemia cells exploit and escape immune cells (T cells) during malignant development.
Antigen-presenting cells are able to internalize cancer cells, and to present parts of these cells on the cell surface. If these parts are recognized by naive T cells as "dangerous", they mature into activated effector T cells which can eliminate all cancer cells. Expression of the molecule PD-L1 on the surface of cancer cells protects these cells from a T cell attack. A therapeutic intervention, for example, by a PD-L1 specific antibody makes the cancer cells again vulnerable to an immune attack and leads to a reduction in cancer cells.
Immune cells not only protect us from invading bacterial and viral pathogens, but also combat transformed malignant cancer cells. The subject of our tumor-immunology research is to decipher the mechanisms by which cancer cells succeed in circumventing clearance by the immune system or even exploit immune cells for tumor growth. In this context, CLL induces an exhausted T cell phenotype marked by Programmed Death 1 (PD1) expression in patients and in the Tcl1 mouse model, which is in the center of our research.
Another focus of our group is the quest for the origin of malignant cells and the nature of the mutations underlying malignant transformation and clonal evolution of tumor cells. In this context, we are especially interested in APOBECs, a group of DNA-deaminating enzymes. APOBECs play a crucial role in the immune system but increasing evidence shows that they are also implicated in lymphomagenesis and clonal cancer evolution due to their DNA-damaging activity.