Interferon Regulatory Factor 4 Regulates the Development of Polymorphonuclear Myeloid-Derived Suppressor Cells Through the Transcription of c-Myc in Cancer
The accumulation of myeloid-derived suppressor cells (MDSCs) is one of the major obstacles to achieve an appropriate anti-tumor immune response and successful tumor immunotherapy. MDSCs in tumor-bearing hosts are primarily polymorphonuclear (PMN-MDSCs). However, the mechanisms regulating the develop...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.627072/full |
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doaj-7bcf3472052b4a6899597d35c6e53ab02021-02-23T04:48:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011210.3389/fimmu.2021.627072627072Interferon Regulatory Factor 4 Regulates the Development of Polymorphonuclear Myeloid-Derived Suppressor Cells Through the Transcription of c-Myc in CancerQuan Yang0Quan Yang1Hongyan Xie2Xing Li3Yuanfa Feng4Shihao Xie5Jiale Qu6Anqi Xie7Yiqiang Zhu8Lu Zhou9Jinxue Yang10Xiaohao Hu11Haixia Wei12Huaina Qiu13Wenjuan Qin14Jun Huang15Jun Huang16The State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Medical Oncology and Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Radiation Oncology, Zhongshan Hospital Affiliated, Xiamen University, Xiamen, ChinaThe State Key Laboratory of Respiratory Disease, The First Affliated Hospital, Guangzhou Medical University, Guangzhou, ChinaSino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, ChinaThe accumulation of myeloid-derived suppressor cells (MDSCs) is one of the major obstacles to achieve an appropriate anti-tumor immune response and successful tumor immunotherapy. MDSCs in tumor-bearing hosts are primarily polymorphonuclear (PMN-MDSCs). However, the mechanisms regulating the development of MDSCs remain poorly understood. In this report, we showed that interferon regulatory factor 4 (IRF4) plays a key role in the development of PMN-MDSCs, but not monocytic MDSCs. IRF4 deficiency caused a significant elevation of PMN-MDSCs and enhanced the suppressive activity of PMN-MDSCs, increasing tumor growth and metastasis in mice. Mechanistic studies showed that c-Myc was up-regulated by the IRF4 protein. Over-expression of c-Myc almost abrogated the effects of IRF4 deletion on PMN-MDSCs development. Importantly, the IRF4 expression level was negatively correlated with the PMN-MDSCs frequency and tumor development but positively correlated with c-Myc expression in clinical cancer patients. In summary, this study demonstrated that IRF4 represents a novel regulator of PMN-MDSCs development in cancer, which may have predictive value for tumor progression.https://www.frontiersin.org/articles/10.3389/fimmu.2021.627072/fullinterferon regulatory factor 4 (IRF4)myeloid-derived suppressor cells (MDSCs)c-Mycimmunosuppressioncancer |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Quan Yang Quan Yang Hongyan Xie Xing Li Yuanfa Feng Shihao Xie Jiale Qu Anqi Xie Yiqiang Zhu Lu Zhou Jinxue Yang Xiaohao Hu Haixia Wei Huaina Qiu Wenjuan Qin Jun Huang Jun Huang |
| spellingShingle |
Quan Yang Quan Yang Hongyan Xie Xing Li Yuanfa Feng Shihao Xie Jiale Qu Anqi Xie Yiqiang Zhu Lu Zhou Jinxue Yang Xiaohao Hu Haixia Wei Huaina Qiu Wenjuan Qin Jun Huang Jun Huang Interferon Regulatory Factor 4 Regulates the Development of Polymorphonuclear Myeloid-Derived Suppressor Cells Through the Transcription of c-Myc in Cancer Frontiers in Immunology interferon regulatory factor 4 (IRF4) myeloid-derived suppressor cells (MDSCs) c-Myc immunosuppression cancer |
| author_facet |
Quan Yang Quan Yang Hongyan Xie Xing Li Yuanfa Feng Shihao Xie Jiale Qu Anqi Xie Yiqiang Zhu Lu Zhou Jinxue Yang Xiaohao Hu Haixia Wei Huaina Qiu Wenjuan Qin Jun Huang Jun Huang |
| author_sort |
Quan Yang |
| title |
Interferon Regulatory Factor 4 Regulates the Development of Polymorphonuclear Myeloid-Derived Suppressor Cells Through the Transcription of c-Myc in Cancer |
| title_short |
Interferon Regulatory Factor 4 Regulates the Development of Polymorphonuclear Myeloid-Derived Suppressor Cells Through the Transcription of c-Myc in Cancer |
| title_full |
Interferon Regulatory Factor 4 Regulates the Development of Polymorphonuclear Myeloid-Derived Suppressor Cells Through the Transcription of c-Myc in Cancer |
| title_fullStr |
Interferon Regulatory Factor 4 Regulates the Development of Polymorphonuclear Myeloid-Derived Suppressor Cells Through the Transcription of c-Myc in Cancer |
| title_full_unstemmed |
Interferon Regulatory Factor 4 Regulates the Development of Polymorphonuclear Myeloid-Derived Suppressor Cells Through the Transcription of c-Myc in Cancer |
| title_sort |
interferon regulatory factor 4 regulates the development of polymorphonuclear myeloid-derived suppressor cells through the transcription of c-myc in cancer |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2021-02-01 |
| description |
The accumulation of myeloid-derived suppressor cells (MDSCs) is one of the major obstacles to achieve an appropriate anti-tumor immune response and successful tumor immunotherapy. MDSCs in tumor-bearing hosts are primarily polymorphonuclear (PMN-MDSCs). However, the mechanisms regulating the development of MDSCs remain poorly understood. In this report, we showed that interferon regulatory factor 4 (IRF4) plays a key role in the development of PMN-MDSCs, but not monocytic MDSCs. IRF4 deficiency caused a significant elevation of PMN-MDSCs and enhanced the suppressive activity of PMN-MDSCs, increasing tumor growth and metastasis in mice. Mechanistic studies showed that c-Myc was up-regulated by the IRF4 protein. Over-expression of c-Myc almost abrogated the effects of IRF4 deletion on PMN-MDSCs development. Importantly, the IRF4 expression level was negatively correlated with the PMN-MDSCs frequency and tumor development but positively correlated with c-Myc expression in clinical cancer patients. In summary, this study demonstrated that IRF4 represents a novel regulator of PMN-MDSCs development in cancer, which may have predictive value for tumor progression. |
| topic |
interferon regulatory factor 4 (IRF4) myeloid-derived suppressor cells (MDSCs) c-Myc immunosuppression cancer |
| url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.627072/full |
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