Age-related increase of tumor susceptibility is associated with myeloid-derived suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred BXD12 mice

Mech Ageing Dev. Nov-Dec 2007;128(11-12):672-80. doi: 10.1016/j.mad.2007.10.003. Epub 2007 Oct 22.

Abstract

In this study, our data show that in young BXD12 mice, the implanted TS/A tumor regressed in 4 weeks after implantation, and this regression was associated with extensive T cell infiltration. In contrast, in old BXD12 mice, it was observed that there was rapid tumor growth by 7 weeks. T cell cytotoxicity against TS/A tumor cells exhibited a significant age-related decline, which was correlated with a decline in CD3(+) T cell infiltration of the tumor. Furthermore, the decline of T cell tumor cytotoxicity in aged BXD12 mice was also correlated with the accumulation of CD11b(+)Gr1(+) myeloid-derived suppressor cells in the spleen. Adoptive transfer of these accumulated CD11b(+)Gr1(+)cells from aged mice to 2-month-old BXD12 mice led to the delay of the rejection of implanted tumor cells. The depletion of CD11b(+)Gr1(+)cells from aged BXD12 mice led to the slower growth of tumor. Induction of arginase 1 in myeloid cells isolated from aged mice plays a partial role in immune suppression of T cell cytotoxicity. Thus, the accumulation of immunosuppresssing myeloid cells appears to contribute to the increase of tumor susceptibility as the age of mice increases.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Age Factors
  • Aging / immunology*
  • Aging / pathology
  • Animals
  • Arginase / biosynthesis
  • CD11 Antigens / analysis
  • CD3 Complex / analysis
  • Cell Line, Tumor
  • Enzyme Induction
  • Female
  • Immune Tolerance*
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Mammary Neoplasms, Animal / immunology*
  • Mammary Neoplasms, Animal / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Myeloid Cells / enzymology
  • Myeloid Cells / immunology*
  • Myeloid Cells / pathology
  • Spleen / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / pathology
  • T-Lymphocytes, Regulatory / enzymology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology
  • Time Factors
  • Tumor Escape*

Substances

  • CD11 Antigens
  • CD3 Complex
  • Arginase