Grant: Project Grant

Lymphoid cancers are the fifth most frequent cancer in humans, affect patients of all ages, and despite generally effective treatments, a significant number of patients will still die of their disease. In certain subgroups of lymphoid cancers, the malignant cells are surrounded by immune cells, yet these cells are unable to muster an effective immune attack against the tumour. In recent years, researchers have made significant progress in understanding how malignant cells evade the immune system. However, this improved knowledge has not yet been successfully translated into better treatments for patients. The research proposed herein focuses on the most common subtype of lymphoma, called diffuse large B cell lymphoma. We will determine how cancer cells gain added "fitness" by acquiring mutations in their genes. Specifically, we will study mutations in the TMEM30A gene that result in accelerated tumor cell growth but as a "side effect" might also lead to increased tumor cell engulfment by specialized immune cells (called macrophages). We will study if this increased engulfment in TMEM30A-mutated lymphomas can be therapeutically exploited, and if novel drugs can further activate this mechanism to eradicate the cancer. Thus, our study might pave the way for novel clinical trials. Furthermore, we will focus on the development of genetic tests that will identify patients at high or low risk of treatment failure with current therapies and the new, investigational drugs. Our studies will be very important for physicians and patients as our research will develop clinical tests that provide information about the prognosis of lymphoma patients and will help develop new drugs and personalized treatments. Ultimately, these treatment improvements will lead to higher cure rates and fewer side effects for patients suffering from lymphomas.