Federico Caligaris-Cappio, MD of Università Vita-Salute San Raffaele, Milan, Italy, disucsses how to removal of macrophages can stop progression of chronic lymphocytic leukemia (CLL) at the 2016 International Workshop of the German CLL Study Group (GCLLSG) in Cologne, Germany. Prof. Caligaris-Cappio explains that CLL cells grow within specific tissues. These tissues are made up of a high number of different normal cells which are utilized by the leukemic cells. He explains that for the last 20 years, research has has been dissecting this microenvironment to identify the most important cells (the cells that help mostly the CLL cells). All different cell populations have been analyzed and it was found that macrophages are the most important cells. Some of these helper macrophages derive from circulating monocytes, which enter lymphoid tissues and mature there into macrophages, which then make physical contact with the leukemic cells and help them proliferate and grow. It is not unlikely that there are also some resident populations of macrophages that have not yet been categorized that do the same job. It has been seen in vivo in animal models that if we get rid of macrophages, there is a significant reduction in the leukemic growth in the mouse. One intelligent way to get rid of macrophages is to use a monoclonal antibody against the key receptor, which is on the surface of macrophages. These monoclonal antibodies work both in mice and in vitro in man but can also be utilized in humans. There are actually a number of trials in solid tumors with this antibody. He predicts that there will also be trials in CLL with the idea that getting rid of macrophages can actually block or hinder the progression of leukemia. Another interesting fact is that when you get rid of macrophages, the leukemic cells within the tissues are pushed out of the tissues and enter the circulating blood. In the mouse, monoclonal antimacrophages have been combined with monoclonal anti-human CD20. He believes that this approach will have a bright future for patients.