Grant: Operating Grant

Primary lymphoid cancer (Hodgkin and non-Hodgkin lymphomas) is the fifth most frequent cancer in humans and affects patients of all ages. These cancers are diverse in their biological and clinical behavior and thus subgroups of lymphomas have been defined. In some of these subgroups many normal cells of the immune system are in direct contact with the malignant cells, yet are unable to kill the cancer cells. Our research group has recently identified that in a subgroup of lymphomas rearrangement of chromosomes (translocations) leading to gene fusions (with genes called CIITA, PDL1 and PDL2) appear to explain some of the mechanisms by which the malignant cells are able to escape the surveillance of the immune system. In the present study we propose to investigate these mutations of the genome in more detail to determine how often these events occur, exactly which genes are involved and by which mechanisms the cells achieve their goal and prevent immune system destruction. We will use staining techniques in lymph node tissue sections and molecular genetic methods to detect changes of the previously identified genes in a large number of cases, and find out if these changes are correlated with the presence of certain immune cells in the direct vicinity of the cancer cells. Furthermore, we will learn if these findings are helpful to predict the prognosis of patients treated with chemotherapy. We will also use modifications to the genome of cultured lymphoma cells to study the mechanistic consequences of our novel findings. Overall, this study will improve our understanding of how lymphoma cells and, likely in more general terms, cancer cells develop into a malignant disease and resist being killed by the patient's immune defence mechanisms. Finally, the results will likely provide cellular targets that can be used for future therapies for patients with malignant lymphoma.