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Rajesh Kumar Sharma, Zinal Chheda, Venkatakrishna Rao Jala, Bodduluri Haribabu, Expression of Leukotriene B4 Receptor-1 on CD8+ T Cells Is Required for Their Migration into Tumors To Elicit Effective Antitumor Immunity, The Journal of Immunology, Volume 191, Issue 6, September 2013, Pages 3462–3470, https://doi.org/10.4049/jimmunol.1300967
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Abstract
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.
