Advances in Anti-Tumor Treatments Targeting the CD47/SIRPα Axis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2020 Feb 22

PMID 32082311

Citations 193

Authors

Wenting Zhang

Qinghua Huang

Weiwei Xiao

Yue Zhao

Jiang Pi

Huan Xu

Hongxia Zhao

Junfa Xu

Colin E Evans

Hua Jin

Affiliations

Soon will be listed here.

Abstract

CD47 is an immunoglobulin that is overexpressed on the surface of many types of cancer cells. CD47 forms a signaling complex with signal-regulatory protein α (SIRPα), enabling the escape of these cancer cells from macrophage-mediated phagocytosis. In recent years, CD47 has been shown to be highly expressed by various types of solid tumors and to be associated with poor patient prognosis in various types of cancer. A growing number of studies have since demonstrated that inhibiting the CD47-SIRPα signaling pathway promotes the adaptive immune response and enhances the phagocytosis of tumor cells by macrophages. Improved understanding in this field of research could lead to the development of novel and effective anti-tumor treatments that act through the inhibition of CD47 signaling in cancer cells. In this review, we describe the structure and function of CD47, provide an overview of studies that have aimed to inhibit CD47-dependent avoidance of macrophage-mediated phagocytosis by tumor cells, and assess the potential and challenges for targeting the CD47-SIRPα signaling pathway in anti-cancer therapy.

Citing Articles

The role of tumor-associated macrophages in lung cancer.

Zhu R, Huang J, Qian F Front Immunol. 2025; 16:1556209.

PMID: 40079009 PMC: 11897577. DOI: 10.3389/fimmu.2025.1556209.

Expression of SIRPα-Fc by oncolytic virus enhances antitumor efficacy through tumor microenvironment reprogramming.

Yang Q, Shu Y, Chen Y, Qi Z, Hu S, Zhang Y Front Immunol. 2025; 16:1513555.

PMID: 40070841 PMC: 11893986. DOI: 10.3389/fimmu.2025.1513555.

Red blood cells-derived components as biomimetic functional materials: Matching versatile delivery strategies based on structure and function.

Liu H, Li Y, Wang Y, Zhang L, Liang X, Gao C Bioact Mater. 2025; 47:481-501.

PMID: 40034412 PMC: 11872572. DOI: 10.1016/j.bioactmat.2025.01.021.

Neutrophil extracellular traps impede cancer metastatic seeding via protease-activated receptor 2-mediated downregulation of phagocytic checkpoint CD24.

Liu Y, Ma J, Ma Y, Wang B, Wang Y, Yuan J J Immunother Cancer. 2025; 13(2).

PMID: 40010762 PMC: 11865804. DOI: 10.1136/jitc-2024-010813.

Therapeutic Applications of Programmed Death Ligand 1 Inhibitors in Small Cell Lung Cancer.

Nabipur L, Mouawad M, Venketaraman V Biomedicines. 2025; 13(2).

PMID: 40002814 PMC: 11852381. DOI: 10.3390/biomedicines13020401.

References

Mohanty S, Yerneni K, Theruvath J, Graef C, Nejadnik H, Lenkov O . Nanoparticle enhanced MRI can monitor macrophage response to CD47 mAb immunotherapy in osteosarcoma. Cell Death Dis. 2019; 10(2):36. PMC: 6367456. DOI: 10.1038/s41419-018-1285-3. View

Uluckan O, Becker S, Deng H, Zou W, Prior J, Piwnica-Worms D . CD47 regulates bone mass and tumor metastasis to bone. Cancer Res. 2009; 69(7):3196-204. PMC: 2763641. DOI: 10.1158/0008-5472.CAN-08-3358. View

Buatois V, Johnson Z, Salgado-Pires S, Papaioannou A, Hatterer E, Chauchet X . Preclinical Development of a Bispecific Antibody that Safely and Effectively Targets CD19 and CD47 for the Treatment of B-Cell Lymphoma and Leukemia. Mol Cancer Ther. 2018; 17(8):1739-1751. PMC: 6072583. DOI: 10.1158/1535-7163.MCT-17-1095. View

Weiskopf K, Ring A, Ho C, Volkmer J, Levin A, Volkmer A . Engineered SIRPα variants as immunotherapeutic adjuvants to anticancer antibodies. Science. 2013; 341(6141):88-91. PMC: 3810306. DOI: 10.1126/science.1238856. View

Chen Q, Wang C, Zhang X, Chen G, Hu Q, Li H . In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment. Nat Nanotechnol. 2018; 14(1):89-97. DOI: 10.1038/s41565-018-0319-4. View

Golubovskaya V, Berahovich R, Zhou H, Xu S, Harto H, Li L . CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth. Cancers (Basel). 2017; 9(10). PMC: 5664078. DOI: 10.3390/cancers9100139. View

Petrova P, Nielsen Viller N, Wong M, Pang X, Lin G, Dodge K . TTI-621 (SIRPαFc): A CD47-Blocking Innate Immune Checkpoint Inhibitor with Broad Antitumor Activity and Minimal Erythrocyte Binding. Clin Cancer Res. 2016; 23(4):1068-1079. DOI: 10.1158/1078-0432.CCR-16-1700. View

Schreiber R, Old L, Smyth M . Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011; 331(6024):1565-70. DOI: 10.1126/science.1203486. View

Jaiswal S, Chao M, Majeti R, Weissman I . Macrophages as mediators of tumor immunosurveillance. Trends Immunol. 2010; 31(6):212-9. PMC: 3646798. DOI: 10.1016/j.it.2010.04.001. View

10.

Yanagita T, Murata Y, Tanaka D, Motegi S, Arai E, Daniwijaya E . Anti-SIRP antibodies as a potential new tool for cancer immunotherapy. JCI Insight. 2017; 2(1):e89140. PMC: 5214103. DOI: 10.1172/jci.insight.89140. View

11.

Yang S, Choi S, Lee J, Park A, Wang K, Phi J . miR-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring through the regulation of DHFR, integrins, and CD47. Oncotarget. 2015; 6(41):43712-30. PMC: 4791261. DOI: 10.18632/oncotarget.6227. View

12.

Marcus A, Gowen B, Thompson T, Iannello A, Ardolino M, Deng W . Recognition of tumors by the innate immune system and natural killer cells. Adv Immunol. 2014; 122:91-128. PMC: 4228931. DOI: 10.1016/B978-0-12-800267-4.00003-1. View

13.

Leclair P, Liu C, Monajemi M, Reid G, Sly L, Lim C . CD47-ligation induced cell death in T-acute lymphoblastic leukemia. Cell Death Dis. 2018; 9(5):544. PMC: 5945676. DOI: 10.1038/s41419-018-0601-2. View

14.

Zeng D, Sun Q, Chen A, Fan J, Yang X, Xu L . A fully human anti-CD47 blocking antibody with therapeutic potential for cancer. Oncotarget. 2016; 7(50):83040-83050. PMC: 5347751. DOI: 10.18632/oncotarget.13349. View

15.

Stengel K, Zheng Y . Cdc42 in oncogenic transformation, invasion, and tumorigenesis. Cell Signal. 2011; 23(9):1415-23. PMC: 3115433. DOI: 10.1016/j.cellsig.2011.04.001. View

16.

Rezaei G, Habibi-Anbouhi M, Mahmoudi M, Azadmanesh K, Moradi-Kalbolandi S, Behdani M . Development of anti-CD47 single-chain variable fragment targeted magnetic nanoparticles for treatment of human bladder cancer. Nanomedicine (Lond). 2017; 12(6):597-613. DOI: 10.2217/nnm-2016-0302. View

17.

Trabulo S, Aires A, Aicher A, Heeschen C, Cortajarena A . Multifunctionalized iron oxide nanoparticles for selective targeting of pancreatic cancer cells. Biochim Biophys Acta Gen Subj. 2017; 1861(6):1597-1605. DOI: 10.1016/j.bbagen.2017.01.035. View

18.

Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B . The Different Mechanisms of Cancer Drug Resistance: A Brief Review. Adv Pharm Bull. 2017; 7(3):339-348. PMC: 5651054. DOI: 10.15171/apb.2017.041. View

19.

Manna P, Frazier W . CD47 mediates killing of breast tumor cells via Gi-dependent inhibition of protein kinase A. Cancer Res. 2004; 64(3):1026-36. DOI: 10.1158/0008-5472.can-03-1708. View

20.

Sick E, Jeanne A, Schneider C, Dedieu S, Takeda K, Martiny L . CD47 update: a multifaceted actor in the tumour microenvironment of potential therapeutic interest. Br J Pharmacol. 2012; 167(7):1415-30. PMC: 3514757. DOI: 10.1111/j.1476-5381.2012.02099.x. View