Is the new angel better than the old devil? Challenges and opportunities in CD47- SIRPα-based cancer therapy

The efficacy of immunotherapies is limited due to the impenetrable nature of the tumor microenvironment (TME). The TME of many tumors is immune-privileged, thus allowing them to evade host immunosurveillance. One mechanism through which this occurs is via the overexpression of CD47, a 'don't eat me' protein that can interact with SIRPα on myeloid cells to suppress their phagocytic action. In recent times, many studies are focusing on CD47-SIRPα-dependent immunotherapies to incite a 'seek and eat' interaction between phagocytes and tumors. Thus, in this review, we highlight the basic molecular properties and mechanisms of CD47-SIRPα cascade. In addition, we discuss the major challenges and potential remedies associated with CD47-SIRPα-based immunotherapies.