Abstract
Accumulation of myeloid-derived suppressor cells (MDSCs) is one of the major obstacles against achieving appropriate anti-tumor immune responses and successful tumor immunotherapy. Granulocytic MDSCs (G-MDSCs) are common in tumor-bearing hosts. However, the mechanisms regulating the development of MDSCs, especially G-MDSCs, remain poorly understood. In this report, we showed that interferon regulatory factor 7 (IRF7) plays an important role in the development of G-MDSCs, but not monocytic MDSCs. IRF7 deficiency caused significant elevation of G-MDSCs, and therefore enhanced tumor growth and metastasis in mice. IRF7 deletion did not affect the suppressive activity of G-MDSCs. Mechanistic studies showed that S100A9, a negative regulator of myeloid cell differentiation, was transrepressed by the IRF7 protein. S100A9 knockdown almost completely abrogated the effects of IRF7 deletion on G-MDSC development and tumor metastasis. Importantly, IRF7 expression levels negatively correlated with the G-MDSC frequency and tumor metastasis, as well as S100A9 expression, in cancer patients. In summary, our study demonstrated that IRF7 represents a novel regulator of G-MDSC development in cancer, which may have predictive value for tumor progression.
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Acknowledgements
This work was supported by the following grants to JZ: National Natural Science Foundation of China (No. 81571520; 91542112; and 31270921), Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (GDUPS, 2014), National Key Basic Research Program of China (No. 2012CB524900), Guangdong Innovative Research Team Program (No. 2009010058), The Fundamental Research Funds for the Central Universities, the Provincial Talents Cultivated by ‘Thousand-Hundred-Ten’ program of Guangdong Province, 111 Project (No. B12003).
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Yang, Q., Li, X., Chen, H. et al. IRF7 regulates the development of granulocytic myeloid-derived suppressor cells through S100A9 transrepression in cancer. Oncogene 36, 2969–2980 (2017). https://doi.org/10.1038/onc.2016.448
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DOI: https://doi.org/10.1038/onc.2016.448
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