CD47, a multi-facetted target for cancer immunotherapy

CD47 is a ubiquitously expressed immunoregulatory protein best known for its so-called 'don't eat me' function that prevents phagocytic removal of healthy cells by the immune system. Many types of cancer present high levels of this don't eat me signal on their surface, thereby disrupting anti-cancer immune responses. Based on this observation, CD47 has become a prominent target in the field of cancer immunotherapy. Indeed, pre-clinical studies have shown therapeutic benefit of anti-CD47 antibodies in solid cancers and most notably B-cell malignancies. However, CD47 is also involved in various other important cellular processes, such as angiogenesis, cancer cell death and regulation of T-cell immunity, which can be modulated via interactions with thrombospondin-1. The therapeutic outcome of CD47-targeted immunotherapy therefore relies on the combined effects of all these processes. Here we will review the various physiological functions of CD47 and their implications in cancer biology. Further, we will review ongoing efforts and provide perspectives for exploiting CD47 as an immunotherapeutic target in cancer.