Liu-Liu Zhao, Rong-Rong Jin, Zhou Fang, Wen Zhang, Guo-Wu Rao, Quan Zheng
Immunotherapy using immune checkpoint inhibitors represents a breakthrough in cancer treatment. The overexpressed CD47 on tumor surfaces functions as a 'don't eat me' signal by binding to signal regulatory protein alpha (SIRPα) on macrophages, facilitating immune escape. However, the advancement of targeted CD47 inhibitors is currently challenged by uncertainties in efficacy, hematological safety, and dosing optimization. This paper provides a comprehensive overview of the structural domains and physiological functions of CD47. We evaluate the current research status of various inhibition strategies, including monoclonal antibodies, fusion proteins, bispecific antibodies, and small-molecule inhibitors, alongside their clinical combinations. The review further addresses developmental hurdles and highlights future prospects in utilizing this target for precision oncotherapy.