Gr-1+CD11b+ cells are responsible for tumor promoting effect of TGF-β in breast cancer progression

Int J Cancer. 2012 Dec 1;131(11):2584-95. doi: 10.1002/ijc.27572. Epub 2012 May 8.


One great challenge in our understanding of TGF-β cancer biology and the successful application of TGF-β-targeted therapy is that TGF-β works as both a tumor suppressor and a tumor promoter. The underlying mechanisms for its functional change remain to be elucidated. Using 4T1 mammary tumor model that shares many characteristics with human breast cancer, particularly its ability to spontaneously metastasize to the lungs, we demonstrate that Gr-1+CD11b+ cells or myeloid derived suppressor cells are important mediators in TGF-β regulation of mammary tumor progression. Depletion of Gr-1+CD11b+ cells diminished the antitumor effect of TGF-β neutralization. Two mechanisms were involved: first, treatment with TGF-β neutralization antibody (1D11) significantly decreased the number of Gr-1+CD11b+ cells in tumor tissues and premetastatic lung. This is mediated through increased Gr-1+CD11b+ cell apoptosis. In addition, 1D11 treatment significantly decreased the expression of Th2 cytokines and Arginase 1. Interestingly, the number and property of Gr-1+CD11b+ cells in peripheral blood/draining lymph nodes correlated with tumor size and metastases in response to 1D11 treatment. Our data suggest that the efficacy of TGF-β neutralization depends on the presence of Gr-1+CD11b+ cells, and these cells could be good biomarkers for TGF-β-targeted therapy.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antibodies, Neutralizing / genetics
  • Antibodies, Neutralizing / immunology
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Arginase / genetics
  • Arginase / immunology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • CD11b Antigen / biosynthesis
  • CD11b Antigen / genetics
  • CD11b Antigen / immunology*
  • Cell Line, Tumor
  • Cytokines / genetics
  • Cytokines / immunology
  • Disease Progression
  • Female
  • Lung / immunology
  • Lung / pathology
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / immunology*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred BALB C
  • Myeloid Cells / immunology
  • Myeloid Cells / pathology
  • Receptors, Chemokine / biosynthesis
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / immunology*
  • Th2 Cells / immunology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology*
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology


  • Antibodies, Neutralizing
  • Biomarkers, Tumor
  • CD11b Antigen
  • Cytokines
  • Gr-1 protein, mouse
  • Receptors, Chemokine
  • Transforming Growth Factor beta
  • Arginase