Macrophage immune checkpoints have recently been exploited to target cancer cells. We have previously reported that targeting the CD47-SIRPA interaction can efficiently eliminate acute myeloid leukemia (AML) stem cells, a novel therapeutic approach that is now investigated in clinical trials (Theocharides et al., Journal of Experimental Medicine 2012). We now aim at further improving this therapeutic approach and at gaining a better understanding of macrophage function in patients.