Breast Cancer Research and Treatment

, Volume 123, Issue 1, pp 39–49

GM-CSF is one of the main breast tumor-derived soluble factors involved in the differentiation of CD11b-Gr1- bone marrow progenitor cells into myeloid-derived suppressor cells

  • Johanna K. Morales
  • Maciej Kmieciak
  • Keith L. Knutson
  • Harry D. Bear
  • Masoud H. Manjili
Preclinical study

DOI: 10.1007/s10549-009-0622-8

Cite this article as:
Morales, J.K., Kmieciak, M., Knutson, K.L. et al. Breast Cancer Res Treat (2010) 123: 39. doi:10.1007/s10549-009-0622-8

Abstract

Recent reports have shown the involvement of tumor burden as well as GM-CSF in supporting myeloid-derived suppressor cells (MDSC). However, it is not known what progenitor cells may differentiate into MDSC in the presence of GM-CSF, and whether FVBN202 transgenic mouse model of spontaneous breast carcinoma may exhibit distinct subset distribution of CD11b+Gr1+ cells. In addition, it is not known why CD11b+Gr1+ cells derived from tumor-free and tumor-bearing animals exhibit different functions. In this study, we determined that GM-CSF was one of the tumor-derived soluble factors that induced differentiation of CD11b-Gr1- progenitor cells from within monocytic/granulocytic bone marrow cells into CD11b+Gr1+ cells. We also showed that CD11b+Gr1+ cells in FVBN202 mice consisted of CD11b+Ly6G-Ly6C+ suppressive and CD11b+Ly6G+Ly6C+ non-suppressive subsets. Previously reported variations between tumor-free and tumor-bearing animals in the function of their CD11b+Gr1+ cells were found to be due to the variations in the proportion of these two subsets. Therefore, increasing ratios of CD11b+Gr1+ cells derived from tumor-free animals revealed their suppressive activity on T cells, in vitro. Importantly, GM-CSF supported the generation of CD11b+Ly6G-Ly6C+ suppressor subsets that inhibited proliferation as well as anti-tumor function of neu-specific T cells. These findings suggest revisiting the use of GM-CSF for the expansion of dendritic cells, ex vivo, for cell-based immunotherapy or as an adjuvant for vaccines for patients with cancer in whom MDSC play a major role in the suppression of anti-tumor immune responses.

Keywords

Myeloid-derived suppressor cells (MDSC) GM-CSF Breast cancer Dendritic cells HER-2/neu 

Supplementary material

10549_2009_622_MOESM1_ESM.pdf (264 kb)
Supplementary material 1 (PDF 264 kb)

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Johanna K. Morales
    • 1
  • Maciej Kmieciak
    • 1
  • Keith L. Knutson
    • 2
  • Harry D. Bear
    • 3
  • Masoud H. Manjili
    • 1
  1. 1.Department of Microbiology & ImmunologyVirginia Commonwealth University School of Medicine, Massey Cancer CenterRichmondUSA
  2. 2.Department of ImmunologyMayo Clinic College of MedicineRochesterUSA
  3. 3.Department of SurgeryVirginia Commonwealth University School of Medicine, Massey Cancer CenterRichmondUSA