Targeting macrophages in classical Hodgkin's lymphoma may seem rational, but is it safe?

A few reports have linked increased numbers of tissue macrophages with treatment failure and reduced lifespan in classical Hodgkin's lymphoma (HL) patients. Some investigators even suggested to target the macrophages in HL with biologic therapy, thus eliminating them from the tumor microenvironment. This review explores the risk: benefit equation of such approach as well as what the author believes is the driving force behind the 'great' migration of macrophages in HL. This article unravels the inflammatory pathways and immune alterations in classical HL that lead to a complex network consisting of T-cells, numerous cytokines, macrophages, and other cells. Macrophages are thought to play a crucial role in tumor antigen processing and presentation tasks, Reed-Sternberg (RS) cell phagocytosis, and antibody-dependent cellular cytotoxicity, therefore their extinction may be hazardous. The author believes RS cells should be targeted by the biologics, not the macrophages, and links his hopes with the existing investigational anti-CD30 therapies in relapsed/refractory classical HL.