Abstract
A promising strategy in tumor immunotherapy is the use of activated dendritic cells as vehicles for tumor vaccines with the goal of activating anti-tumor T cell responses. Current formulations for dendritic cell-based immunotherapies have limited effects on patient survival, providing motivation for further investigation of ways to enhance dendritic cell priming of anti-tumor T cell responses. Using a brief in vitro priming model, we have found that B7-H1 expressed by activated dendritic cells is integrated during priming of naïve CD8+ T cells and functions to limit the differentiation of effector T cell responses. CD8+ T cells primed by B7-H1-deficient dendritic cells exhibit increased production of IFN-γ, enhanced target cell killing, and improved anti-tumor activity. Additionally, enhanced memory populations arise from CD8+ T cells primed by B7-H1-deficient dendritic cells. Based on these findings, we suggest that early blockade of B7-H1 signaling should be investigated as a strategy to improve dendritic cell-based anti-tumor immunotherapy.
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Abbreviations
- B6:
-
C57BL6
- BM:
-
Bone marrow
- CTL:
-
Cytotoxic T lymphocyte
- KO:
-
Knock out
- MFI:
-
Mean fluorescence intensity
- WT:
-
Wild type
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Acknowledgments
We are thankful to Tian Tian (Harvard University) for providing OT-1 Thy 1.1+ mice, Lieping Chen (Yale University) for providing B7-H1 KO mice, G4 hybridoma cells, and 10B5 hybridoma cells, Dr. Koji Tamada for anti-B7-H1 (43H12) monoclonal antibody, and Richard Vile (Mayo Clinic) for providing B16-OVA tumor cells. This work was supported by the American Cancer Society’s New Investigator Award, the Wendy Case Cancer Research Fund, and in part by the National Institutes of Health (RO1 CA134345).
Conflict of interest
Eugene. D. Kwon, Haidong Dong, and Mayo Clinic have a financial conflict of interest related to this research (Patents of B7-H1 as a cancer prognostic marker). This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic conflict of interest policies. The other authors have no financial conflicts of interest.
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Drs. Eugene D. Kwon and Haidong Dong share senior authorship.
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Gibbons, R.M., Liu, X., Harrington, S.M. et al. B7-H1 signaling is integrated during CD8+ T cell priming and restrains effector differentiation. Cancer Immunol Immunother 63, 859–867 (2014). https://doi.org/10.1007/s00262-014-1563-6
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DOI: https://doi.org/10.1007/s00262-014-1563-6