The innate immune system forms the body’s first line of defense against invaders but its potential to fight tumors has long been ignored. Our SIRPαFc decoy receptors are designed to activate cells of the innate immune system to phagocytose and destroy tumor cells. This effect is seen across a range of both blood and solid cancers. In addition to their direct anti-tumor activity, cells of the innate immune system play a key role in recruiting and activating the adaptive immune system, which provides specificity and memory. We envision a mechanism by which SIRPαFc blocks the CD47 “don’t eat me” signal and engages activating Fc receptors on macrophages, leading to tumor cell phagocytosis, increased antigen presentation and enhanced T cell responses, thus bridging both innate and adaptive immunity (see figure).