CD47: the next checkpoint target for cancer immunotherapy

Cancer immunotherapy using checkpoint blockade has brought about a paradigm shift in the treatment of advanced-stage cancers. Unfortunately, not all patients benefit from these therapies, paving the way for other immune checkpoints to be targeted. CD47, a 'marker-of-self' protein that is overexpressed broadly across tumor types, is emerging as a novel potent macrophage immune checkpoint for cancer immunotherapy. Recently, CD47 blockade by Hu5F9-G4 has shown promise combined with Rituximab in non-Hodgkin's lymphoma. Here we review the complex structure and various physiological functions of CD47 and their implications in cancer biology. Further, this review considers future directions and challenges in advancing this promising target platform to widespread therapeutic use.