Deletion of TGF-β signaling in myeloid cells enhances their anti-tumorigenic properties

J Leukoc Biol. 2012 Sep;92(3):641-51. doi: 10.1189/jlb.1211639. Epub 2012 Jun 8.


By crossing LysM-Cre and TGF-β type II receptor (Tgfbr2) floxed mice we achieved specific deletion of Tgfbr2 in myeloid cells (Tgfbr2(MyeKO) mice). S.c.-injected (LLC, EL4-OVA) and implanted (MMTV-PyMT) carcinoma cells grow slower in Tgfbr2(MyeKO) mice. The number of CD45(+) cells in the tumor tissue was the same in both genotypes of mice, but upon analysis, the percentage of T cells (CD45(+)CD3(+)) in the KO mice was increased. By flow cytometry analysis, we did not detect any differences in the number and phenotype of TAMs, CD11b(+)Gr1(+), and DCs in Tgfbr2(MyeKO) compared with Tgfbr2(MyeWT) mice. ELISA and qRT-PCR data showed differences in myeloid cell functions. In Tgfbr2(MyeKO) TAMs, TNF-α secretion was increased, basal IL-6 secretion was down-regulated, TGF-β did not induce any VEGF response, and there was decreased MMP9 and increased MMP2 and iNOS expression. TGF-β did not have any effect on CD11b(+)Gr1(+) cells isolated from Tgfbr2(MyeKO) mice in the regulation of Arg, iNOS, VEGF, and CXCR4, and moreover, these cells have decreased suppressive activity relative to T cell proliferation. Also, we found that DCs from tumor tissue of Tgfbr2(MyeKO) mice have increased antigen-presented properties and an enhanced ability to stimulate antigen-specific T cell proliferation. We conclude that Tgfbr2 in myeloid cells has a negative role in the regulation of anti-tumorigenic functions of these cells, and deletion of this receptor decreases the suppressive function of CD11b(+)Gr1(+) cells and increases antigen-presenting properties of DCs and anti-tumorigenic properties of TAMs.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Cell Separation
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Knockout
  • Myeloid Cells / immunology*
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / immunology*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / immunology*
  • Protein Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / immunology*
  • Receptors, Transforming Growth Factor beta / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology


  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II