Grant: CIHR New Investigator

Malignant lymphomas are the fifth most frequent cancer in humans, affect patients of all ages, and despite generally effective treatments, a significant number of patients still die of their disease. In certain subgroups of lymphoma, the malignant cells are surrounded by normal immune cells, yet these cells are unable to muster an effective immune attack against the tumor. In recent years, researchers have made significant progress in understanding how the malignant cells are evading the immune system. However, this improved knowledge has not yet been successfully translated into better treatments for patients. The herein proposed research focuses on two related subtypes of lymphoma - called Hodgkin lymphoma and Primary mediastinal B-cell lymphoma - that often affect adolescents and young adults. We will study the exact mechanisms of immune system escape investigating certain genes that we have found altered in earlier studies. We will focus on the effect of these alterations on tumor surrounding immune cells and on macrophages (a type of white blood cells that ingests foreign material) in particular, in order to characterize novel drug targets and to pave the way for innovative clinical trials. Using state-of-the art genome-wide sequencing methods we will also define the complete landscape of genetic alterations in Hodgkin lymphoma and primary mediastinal B cell lymphoma. Furthermore, we will focus on the development of genetic tests that predict therapy resistance in childhood and adult Hodgkin lymphoma and identify patients at high risk of relapse. Our studies will be very important for physicians and patients as our research will develop clinical tests that provide information about the individual prognosis of lymphoma patient and will help developing new drugs and personalized treatments. Ultimately, these treatment improvements will lead to higher cure rates and fewer side effects for patients suffering from malignant lymphomas.