Frontiers in Immunology (Feb 2021)

Interferon Regulatory Factor 4 Regulates the Development of Polymorphonuclear Myeloid-Derived Suppressor Cells Through the Transcription of c-Myc in Cancer

  • 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

DOI
https://doi.org/10.3389/fimmu.2021.627072
Journal volume & issue
Vol. 12

Abstract

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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.

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