Expression of leukotriene B₄ receptor-1 on CD8⁺ T cells is required for their migration into tumors to elicit effective antitumor immunity.

Leukotriene B₄ (LTB₄) 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-γ, 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.