In our investigation, we observed that the LSCs IL-33/Il1rl1 autocrine loop fosters tolerance by the immune microenvironment, and disruption of the IL-33/Il1rl1 signaling solely in the LSCs can reverse this tolerance by increasing type 1 CD8+ T cells, especially those specific for the leukemia WT-1 antigen, while decreasing Tregs, macrophages and MDSCs. The gene discussed is IL1RL1; the disease is leukemia.