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

Academic Article

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.
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    Keywords

  • Adoptive Transfer, Age Factors, Aging, Animals, Arginase, CD11 Antigens, CD3 Complex, Cell Line, Tumor, Enzyme Induction, Female, Immune Tolerance, Lymphocytes, Tumor-Infiltrating, Mammary Neoplasms, Animal, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Myeloid Cells, Spleen, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Regulatory, Time Factors, Tumor Escape
  • Digital Object Identifier (doi)

    Author List

  • Grizzle WE; Xu X; Zhang S; Stockard CR; Liu C; Yu S; Wang J; Mountz JD; Zhang H-G
  • Start Page

  • 672
  • End Page

  • 680
  • Volume

  • 128
  • Issue

  • 11-12