The Lymphoma Microenvironment – Prof. Davide Rossi (IOR)

Understanding how clonal hematopoiesis feeds lymphoma

Patients with lymphoma who do not respond to treatment have a bleak outcome. Annually, over 1100 patients die with leukemia and lymphoma in Switzerland. Lymphoma can arise when the DNA inside a lymphocyte changes in a way that prevents the lymphocyte from responding to signals that usually keep it under control. To outgrow and disseminate, lymphoma hijacks normal inflammatory cells to acquire protection and nurturing, while at the same time deceiving them by hiding from their attack. Inflammation may be age-related and can foster manifestations such as clonal hematopoiesis or can be sustained by chronic infections of the lymphoma cell itself.

The new avenues of lymphoma therapy rely on a combination of approaches that target both tumor cells and the supporting host environment, including: i) repairing the operative system inside lymphoma cells, which can be achieved by using small molecules that precisely identify and attack the factors that led to its failure; ii) reverting the stunned inflammatory cells from lymphoma feeders to lymphoma predators. The experiments will also allow us to understand how aging-related inflammation facilitates lymphoma development. We aim to understand how aging of the normal immune functions (designed to cause inflammation) modulate the tumor and the surrounding immune system. Single cell resolution now puts us in the unique position to track the aging of cells of the immune system (locally and globally) and to connect them to the behavior of cancer cells. We will use this knowledge to develop strategies to engage the healthy immune compartment in the fight against the tumor. This is of particular interest as the advent of multiple immunotherapy approaches puts increasing emphasis on the efficacy of drugs on immune responses or the fitness (exhaustion) of the anti-tumor response.