Age-related increase of tumor susceptibility is associated with myeloid-derived suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred BXD12 mice.
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.
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.
William E
WE
Grizzle
Xin
X
Xu
Shuangqin
S
Zhang
Cecil R
CR
Stockard
Cunren
C
Liu
Shaohua
S
Yu
Jianhua
J
Wang
John D
JD
Mountz
Huang-Ge
HG
Zhang
D019264:Adoptive Transfer; D000367:Age Factors; D000375:Aging / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001119:Arginase / Q000096:biosynthesis; D018845:CD11 Antigens / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D045744:Cell Line, Tumor; D004790:Enzyme Induction; D005260:Female; D007108:Immune Tolerance; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D022423:Myeloid Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D013997:Time Factors; D019139:Tumor Escape
D018845:CD11 Antigens; D017252:CD3 Complex; D001119:Arginase