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.
Grizzle
William E
WE
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294-0007, USA.
Xu
Xin
X
Zhang
Shuangqin
S
Stockard
Cecil R
CR
Liu
Cunren
C
Yu
Shaohua
S
Wang
Jianhua
J
Mountz
John D
JD
Zhang
Huang-Ge
HG
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