Acceleration of tumor growth due to dysfunction in M1 macrophages and enhanced angiogenesis in an animal model of autoimmune disease

Lab Invest. 2016 Apr;96(4):468-80. doi: 10.1038/labinvest.2015.166. Epub 2016 Jan 25.


Both autoimmunity and tumor immunity are immune responses against self-tissues or cells. However, the precise similarity or difference between them remains unclear. In this study, to understand a novel mechanism of tumor immunity, we performed transplantation experiments with a murine autoimmune model, C57BL/6J (B6)/lpr mice. A melanoma cell line, B16F10 cells, or granulocyte macrophage colony-stimulating factor- overexpressing B16F10 (B16F10/mGM) cells were transplanted into B6 or B6/lpr mice. Tumor growth by transplanted B16F10/mGM cells was significantly accelerated in B6/lpr mice compared with that in B6 mice. The accumulation of M1 macrophages in the tumor tissues of B6/lpr recipient mice was significantly lower compared with that in the control mice. In vitro co-culture experiment showed that impaired differentiation into M1 macrophages was observed in B6/lpr mice. The number of tumor vessels and vascular endothelial growth factor (VEGF) expression were also significantly enhanced in the tumor tissues of B6/lpr mice compared with those in the B6 mice. Moreover, VEGF expression was correlated with the increased expression of hypoxia-inducible factor-1α in the tumor tissues of B6/lpr mice. These results suggest that dysfunctional tumor immunity and enhanced angiogenesis in autoimmunity influence tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Cell Line, Tumor
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / immunology
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunohistochemistry
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Macrophage Colony-Stimulating Factor / genetics
  • Macrophage Colony-Stimulating Factor / immunology
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Macrophages / classification
  • Macrophages / immunology*
  • Melanoma, Experimental / blood supply
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / immunology*
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / immunology*
  • Neovascularization, Pathologic / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Burden / genetics
  • Tumor Burden / immunology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / immunology
  • Vascular Endothelial Growth Factor A / metabolism


  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Macrophage Colony-Stimulating Factor
  • Interferon-gamma