Myeloid-Derived Suppressor Cell Subsets Drive Glioblastoma Growth in a Sex-Specific Manner

Cancer Discov. 2020 Aug;10(8):1210-1225. doi: 10.1158/2159-8290.CD-19-1355. Epub 2020 Apr 16.


Myeloid-derived suppressor cells (MDSC) that block antitumor immunity are elevated in glioblastoma (GBM) patient blood and tumors. However, the distinct contributions of monocytic (mMDSC) versus granulocytic (gMDSC) subsets have yet to be determined. In mouse models of GBM, we observed that mMDSCs were enriched in the male tumors, whereas gMDSCs were elevated in the blood of females. Depletion of gMDSCs extended survival only in female mice. Using gene-expression signatures coupled with network medicine analysis, we demonstrated in preclinical models that mMDSCs could be targeted with antiproliferative agents in males, whereas gMDSC function could be inhibited by IL1β blockade in females. Analysis of patient data confirmed that proliferating mMDSCs were predominant in male tumors and that a high gMDSC/IL1β gene signature correlated with poor prognosis in female patients. These findings demonstrate that MDSC subsets differentially drive immune suppression in a sex-specific manner and can be leveraged for therapeutic intervention in GBM. SIGNIFICANCE: Sexual dimorphism at the level of MDSC subset prevalence, localization, and gene-expression profile constitutes a therapeutic opportunity. Our results indicate that chemotherapy can be used to target mMDSCs in males, whereas IL1 pathway inhibitors can provide benefit to females via inhibition of gMDSCs.See related commentary by Gabrilovich et al., p. 1100.This article is highlighted in the In This Issue feature, p. 1079.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / immunology
  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Coculture Techniques
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / immunology
  • Glioblastoma / pathology*
  • Humans
  • Immunotherapy
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / genetics
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid-Derived Suppressor Cells* / drug effects
  • Sex Characteristics*
  • T-Lymphocytes / immunology
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use


  • Antineoplastic Agents
  • IL1B protein, mouse
  • Interleukin-1beta
  • Vidarabine
  • fludarabine