Deciphering the role of CD47 in cancer immunotherapy

Graphical abstract

Highlights

• •

  CD47 has emerged as a target in cancer immunotherapy.

• •

  CD47 is highly expressed in cancers to prevent phagocytosis by phagocytes.

• •

  Targeting CD47 has been verified as a promising therapeutic strategy in cancer immunotherapy.

• •

  Antibodies and small molecules targeting CD47 exhibited both safety and efficacy in clinical trials.

• •

  Formidable challenges of targeting CD47 including anemia can be avoided by targeting the regulators of CD47 or its receptor SIRPα.

Abstract

Background

Immunotherapy has emerged as a novel strategy for cancer treatment following surgery, radiotherapy, and chemotherapy. Immune checkpoint blockade and Chimeric antigen receptor (CAR)-T cell therapies have been successful in clinical trials. Cancer cells evade immune surveillance by hijacking inhibitory pathways via overexpression of checkpoint genes. The Cluster of Differentiation 47 (CD47) has emerged as a crucial checkpoint for cancer immunotherapy by working as a “don’t eat me” signal and suppressing innate immune signaling. Furthermore, CD47 is highly expressed in many cancer types to protect cancer cells from phagocytosis via binding to SIRPα on phagocytes. Targeting CD47 by either interrupting the CD47-SIRPα axis or combing with other therapies has been demonstrated as an encouraging therapeutic strategy in cancer immunotherapy. Antibodies and small molecules that target CD47 have been explored in pre- and clinical trials. However, formidable challenges such as the anemia and palate aggregation cannot be avoided because of the wide presentation of CD47 on erythrocytes.

Aim of view

This review summarizes the current knowledge on the regulation and function of CD47, and provides a new perspective for immunotherapy targeting CD47. It also highlights the clinical progress of targeting CD47 and discusses challenges and potential strategies.

Key scientific concepts of review

This review provides a comprehensive understanding of targeting CD47 in cancer immunotherapy, it also augments the concept of combination immunotherapy strategies by employing both innate and adaptive immune responses.