Regulation of CD47 expression by interferon-gamma in cancer cells
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 in...
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2021-09-01
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Series: | Translational Oncology |
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doaj-4bd8fe6000854940a31db4ecffc750f32021-07-15T04:27:11ZengElsevierTranslational Oncology1936-52332021-09-01149101162Regulation of CD47 expression by interferon-gamma in cancer cellsZi-Han Ye0Xiao-Ming Jiang1Mu-Yang Huang2Yu-Lian Xu3Yu-Chi Chen4Luo-Wei Yuan5Can-Yu Huang6Wei-Bang Yu7Xiuping Chen8Jin-Jian Lu9State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China; MoE Frontiers Science Center for Precision Oncology, University of Macau, Macao, China; Corresponding author at: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, ChinaThe 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.http://www.sciencedirect.com/science/article/pii/S1936523321001546 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zi-Han Ye Xiao-Ming Jiang Mu-Yang Huang Yu-Lian Xu Yu-Chi Chen Luo-Wei Yuan Can-Yu Huang Wei-Bang Yu Xiuping Chen Jin-Jian Lu |
spellingShingle |
Zi-Han Ye Xiao-Ming Jiang Mu-Yang Huang Yu-Lian Xu Yu-Chi Chen Luo-Wei Yuan Can-Yu Huang Wei-Bang Yu Xiuping Chen Jin-Jian Lu Regulation of CD47 expression by interferon-gamma in cancer cells Translational Oncology |
author_facet |
Zi-Han Ye Xiao-Ming Jiang Mu-Yang Huang Yu-Lian Xu Yu-Chi Chen Luo-Wei Yuan Can-Yu Huang Wei-Bang Yu Xiuping Chen Jin-Jian Lu |
author_sort |
Zi-Han Ye |
title |
Regulation of CD47 expression by interferon-gamma in cancer cells |
title_short |
Regulation of CD47 expression by interferon-gamma in cancer cells |
title_full |
Regulation of CD47 expression by interferon-gamma in cancer cells |
title_fullStr |
Regulation of CD47 expression by interferon-gamma in cancer cells |
title_full_unstemmed |
Regulation of CD47 expression by interferon-gamma in cancer cells |
title_sort |
regulation of cd47 expression by interferon-gamma in cancer cells |
publisher |
Elsevier |
series |
Translational Oncology |
issn |
1936-5233 |
publishDate |
2021-09-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S1936523321001546 |
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