Expression of Leukotriene B4 receptor 1 on CD8+ T cells is essential for their migration to tumors, immune-surveillance and cancer immunity (P5106)

Abstract

Abstract The role of Leukotriene B4 (LTB4) receptor 1, BLT1 as a pro-inflammatory mediator in various inflammatory diseases is well known. However, its role in regulating immune responses to tumor is yet unknown. Here, we studied the role of BLT1 in CD8+ T cell mediated anti-tumor response using implantable TC-1 cervical cancer and B16F10 melanoma mice models. BLT1−/− mice had significantly accelerated tumor growth, reduced survival, and decreased CD8+ T cells as well as their effector molecules such as IFN-γ, granzyme-B and IL-2 within tumors as shown by flow cytometry and confocal microscopy, compared to the WT controls. Moreover, the tumor growth patterns in BLT1−/− mice was similar to WT mice that were depleted of their CD8+ T cells. Evaluation of CTL responses by in vivo killing assay revealed no differences in the cytolytic ability between WT and BLT1-/- CD8+ T cells. Adoptive transfer of tumor primed CD8+ T cells from WT but not BLT1-/- mice reduced tumor growth in Rag2-/- mice. In Rag2-/- mice, while the numbers of WT or BLT1-/- CD8+ T cells in dLN remain similar, the recruitment of BLT1-/- CD8+ T cells into tumor was dramatically reduced as compared to WT CD8+ T cells. Analysis of CD8+ T cells from the dLN revealed no difference in the expression of other T cell chemokine receptors. These results demonstrate a previously unidentified, yet crucial role of BLT1 on CD8+ T cell in their effective migration into the tumor and hence in immune-surveillance and anti-tumor immunity.