CD47, a multi-facetted target for cancer immunotherapy

Abstract

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.

Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis

“…The CD47/SIRP-α axis has been established as an important regulator of innate anti-cancer immunity, with many if not all malignancies overexpressing the receptor CD47 that binds to phagocyte-expressed SIRP-α 1–3 . CD47-mediated triggering of SIRP-α inhibits phagocytic removal of cancer cells and reduces the immunogenic processing of cancer cells by macrophages and dendritic cells 2,4,5 .…”

Does cancer cell-expressed SLAMF7 impact on CD47-mediated phagocytosis?

“…Specifically, SIRP-α is an immunoreceptor tyrosine-based inhibitory motiv (ITIM)containing ligand that upon triggering inhibits phagocyte activity and reduces the immunogenic processing of cancer cells, leading to inhibition of not only innate but also adaptive immune responses. 1 Antibodies that block the interaction of CD47 with SIRP-α can therapeutically augment phagocytosis of cancer cells, if and when the balance of pro and antiphagocytic signals is sufficiently shifted towards phagocytic uptake. 2 More importantly, co-treatment of anticancer monoclonal antibodies with CD47 blocking antibodies augments therapeutic anticancer activity in vivo and in vitro.…”