| First Author | Sharma RK | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 6 | Pages | 3462-70 |
| PubMed ID | 23960231 | Mgi Jnum | J:205870 |
| Mgi Id | MGI:5546555 | Doi | 10.4049/jimmunol.1300967 |
| Citation | Sharma RK, et al. (2013) Expression of leukotriene B(4) receptor-1 on CD8(+) T cells is required for their migration into tumors to elicit effective antitumor immunity. J Immunol 191(6):3462-70 |
| abstractText | Leukotriene B(4) (LTB(4)) receptor (BLT)1 is expressed on variety of immune cells and has been implicated as a mediator of diverse inflammatory diseases. However, whether biological responses initiated via this receptor generate tumor-promoting inflammation or antitumor immunity remains unexplored. In this study, we investigated the role of BLT1 in antitumor immunity using syngeneic TC-1 cervical cancer model, and observed accelerated tumor growth and reduced survival in BLT1(-)/(-) mice compared with BLT1(+)/(+) mice. Analysis of the tumor infiltrates by flow cytometry and confocal microscopy revealed a significant decrease in effector immune cells, most notably, CD8(+) T cells and NK cells in the tumors of the BLT1(-)/(-) mice. Gene expression profiling confirmed the dramatic decrease of IFN-gamma, granzyme B, and IL-2 in tumors growing in BLT1(-)/(-) mice. Furthermore, depletion of CD8(+) T cells enhanced the tumor growth in BLT1(+)/(+) but not in BLT1(-)/(-) mice. However, similar levels of Ag-dependent CD8(+) T cell-mediated killing activity were observed in spleens of BLT1(+)/(+) and BLT1(-)/(-) mice. Adoptive transfer of CD8(+) T cells from tumor-bearing BLT1(+)/(+) but not BLT1(-)/(-) mice significantly reduced tumor growth and increased the survival of Rag2(-)/(-) mice. Although the homeostatic proliferation and expression profiles of other chemokine receptors of adoptively transferred BLT1(+)/(+) and BLT1(-)/(-) CD8(+) T cells appears to be similar, BLT1(+)/(+) T lymphocytes entered the tumors in greater numbers. These results suggest that BLT1 expression on CD8(+) T cells plays an important role in their trafficking to tumors. |
