Quercetin promotes the survival of granulocytic myeloid-derived suppressor cells via the ESR2/STAT3 signaling pathway

Biomed Pharmacother. 2020 May:125:109922. doi: 10.1016/j.biopha.2020.109922. Epub 2020 Jan 31.

Abstract

Quercetin is a natural product that has been shown to induce tumor apoptosis and necrosis through multiple mechanisms. Tumor-induced myeloid-derived suppressor cell (MDSC) expansion negatively regulates the immune response by inhibiting T cell function through signal transducer and activator of transcription 3 (STAT3) activation, thereby facilitating tumor escape from host immune surveillance. Thus MDSC is an attractive target for cancer immunotherapy to enhance cytotoxic T cell responses. However, the effects of quercetin on MDSC are poorly understood. Here, we demonstrate that quercetin treatment enhanced mouse- and human- derived granulocytic-myeloid-derived suppressor cells (G-MDSC) survival and promoted the secretion of T cell-suppressive factors in vitro. Bioinformatics analysis further showed that quercetin was highly correlated with the estrogen receptor signaling pathway, which was confirmed by quantitative reverse transcription-polymerase chain reaction and flow cytometric analysis. These findings highlight the potential advantages and feasibility of quercetin in reinforcing the suppressive property of G-MDSC. Thus impact of G-MDSC should be taken into consideration when quercetin is applied to tumor therapy.

Keywords: Cell survival; Estrogen receptors; Myeloid-derived suppressor cell; Quercetin.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Estrogen Receptor beta / metabolism*
  • Fetal Blood / drug effects
  • Fetal Blood / metabolism
  • Granulocytes / drug effects
  • Granulocytes / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myeloid-Derived Suppressor Cells / drug effects
  • Myeloid-Derived Suppressor Cells / metabolism*
  • Quercetin / pharmacology*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Antioxidants
  • ESR2 protein, human
  • Estrogen Receptor beta
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Quercetin