Tumor-induced myeloid-derived suppressor cell function is independent of IFN-γ and IL-4Rα

Eur J Immunol. 2012 Aug;42(8):2052-9. doi: 10.1002/eji.201142230.


Myeloid-derived suppressor cells (MDSCs) are present in most cancer patients and experimental animals where they exert a profound immune suppression and are a significant obstacle to immunotherapy. IFN-γ and IL-4 receptor alpha (IL-4Rα) have been implicated as essential molecules for MDSC development and immunosuppressive function. If IFN-γ and IL-4Rα are critical regulators of MDSCs, then they are potential targets for preventing MDSC accumulation or inhibiting MDSC function. Because data supporting a role for IFN-γ and IL-4Rα are not definitive, we have examined MDSCs induced in IFN-γ-deficient, IFN-γR-deficient, and IL-4Rα-deficient mice carrying three C57BL/6-derived (B16 melanoma, MC38 colon carcinoma, and 3LL lung adenocarcinoma), and three BALB/c-derived (4T1 and TS/A mammary carcinomas, and CT26 colon carcinoma) tumors. We report that although MDSCs express functional IFN-γR and IL-4Rα, and have the potential to signal through the STAT1 and STAT6 pathways, respectively, neither IFN-γ nor IL-4Rα impacts the phenotype, accumulation, or T-cell suppressive potency of MDSCs, although IFN-γ and IL-4Rα modestly alter MDSC-macrophage IL-10 crosstalk. Therefore, neither IFN-γ nor IL-4Rα is a key regulator of MDSCs and targeting these molecules is unlikely to significantly alter MDSC accumulation or function.

Publication types

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

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma of Lung
  • Animals
  • Colonic Neoplasms / immunology
  • Female
  • Immune Tolerance*
  • Interferon-gamma / deficiency
  • Interferon-gamma / metabolism*
  • Interleukin-10
  • Interleukin-4 Receptor alpha Subunit / deficiency
  • Interleukin-4 Receptor alpha Subunit / metabolism*
  • Lung Neoplasms / immunology
  • Lymphocyte Activation
  • Macrophages / immunology
  • Mammary Neoplasms, Animal / immunology
  • Melanoma / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid Cells / immunology*
  • Myeloid Cells / metabolism


  • Interleukin-4 Receptor alpha Subunit
  • Interleukin-10
  • Interferon-gamma