 Two signatures of the microenvironment were recently identified that are predictive of outcome in patients with newly diagnosed DLBCL treated with R-CHOP. These signatures, called stromal 1 and stromal 2 , are associated with genes expressed by infiltrating mononuclear cells. The stromal 2 signature, which includes genes associated with angiogenesis, is predictive of an inferior outcome. Based on these observations, we are interested in targeting the reactive cells in the microenvironment as a therapeutic strategy in patients with relapsed and refractory DLBCL. Along the same principles, we are also including patients with relapsed Hodgkin lymphoma HL. The surrounding reactive cells around Hodgkin Reed Sternberg HRS cells are now not thought to be bystander cells and they appear to provide important survival signals to HRS cells. 