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Regulation of CD47 expression by interferon-gamma in cancer cells
Ye, Zi Han1; Jiang, Xiao Ming1; Huang, Mu Yang1; Xu, Yu Lian1; Chen, Yu Chi1; Yuan, Luo Wei1; Huang, Can Yu1; Yu, Wei Bang1; Chen, Xiuping1; Lu, Jin Jian1,2
2021-09-01
Source PublicationTranslational Oncology
ISSN1936-5233
Volume14Issue:9
Abstract

The anti-phagocytosis signal, CD47, prevents phagocytosis when it interacts with signal-regulatory protein alpha (SIRPα) on macrophages. Given the vital role of CD47 in immune response, further investigation on the regulation of CD47 in tumor microenvironment is needed. Herein, we identified that interferon-gamma (IFN-γ), one of the most important cytokines in the immune and inflammatory response, up-regulated CD47 expression in cancer cells and this effect could be inhibited by the JAK1/2 inhibitor ruxolitinib, as well as siRNA-mediated silencing of JAK1, STAT1, and IRF1. The IFN-γ-induced surface expression of CD47 contributed to a stronger binding affinity to SIRPα and a decrease in phagocytosis of cancer cells by macrophages. Knockdown of JAK1, STAT1, or IRF1 by siRNA reversed the decreased phagocytosis caused by IFN-γ. Besides, analysis from TCGA revealed that IFNG had a positive correlation with CD47 in various types of cancer, which was supported by the increased surface CD47 expression after IFN-γ treatment in different types of cancer cells. The discovery of IFN-γ-induced up-regulation of CD47 in cancer cells unveils another feedback inhibitory mechanism of IFN-γ, thus providing insights into cancer immunotherapy targeting CD47.

DOI10.1016/j.tranon.2021.101162
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000687285600001
Scopus ID2-s2.0-85108419682
Fulltext Access
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorLu, Jin Jian
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.MoE Frontiers Science Center for Precision Oncology, University of Macau, Macao, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences;  University of Macau
Recommended Citation
GB/T 7714
Ye, Zi Han,Jiang, Xiao Ming,Huang, Mu Yang,et al. Regulation of CD47 expression by interferon-gamma in cancer cells[J]. Translational Oncology,2021,14(9).
APA Ye, Zi Han,Jiang, Xiao Ming,Huang, Mu Yang,Xu, Yu Lian,Chen, Yu Chi,Yuan, Luo Wei,Huang, Can Yu,Yu, Wei Bang,Chen, Xiuping,&Lu, Jin Jian.(2021).Regulation of CD47 expression by interferon-gamma in cancer cells.Translational Oncology,14(9).
MLA Ye, Zi Han,et al."Regulation of CD47 expression by interferon-gamma in cancer cells".Translational Oncology 14.9(2021).
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