title: Expression of leukotriene B₄ receptor-1 on CD8⁺ T cells is required for their migration into tumors to elicit effective antitumor immunity.
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.
authors: James Graham Brown Cancer Center, University of Louisville Health Sciences, Louisville, KY 40202, USA.
authors: Rajesh Kumar
authors: RK
authors: Sharma
authors: Zinal
authors: Z
authors: Chheda
authors: Venkatakrishna Rao
authors: VR
authors: Jala
authors: Bodduluri
authors: B
authors: Haribabu
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016246:Lymphocytes, Tumor-Infiltrating; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D060888:Real-Time Polymerase Chain Reaction; D018102:Receptors, Leukotriene B4 / Q000096:biosynthesis*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000378:metabolism
chemical_list: C503704:Ltb4r1 protein, mouse; D018102:Receptors, Leukotriene B4
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