B7-H1 signaling is integrated during CD8 super(+) T cell priming and restrains effector differentiation
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...
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Published in | Cancer Immunology, Immunotherapy Vol. 63; no. 8; pp. 859 - 867 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
01.08.2014
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Online Access | Get full text |
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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 naive CD8 super(+) T cells and functions to limit the differentiation of effector T cell responses. CD8 super(+) T cells primed by B7-H1-deficient dendritic cells exhibit increased production of IFN- gamma , enhanced target cell killing, and improved anti-tumor activity. Additionally, enhanced memory populations arise from CD8 super(+) 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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AbstractList | 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 naive CD8 super(+) T cells and functions to limit the differentiation of effector T cell responses. CD8 super(+) T cells primed by B7-H1-deficient dendritic cells exhibit increased production of IFN- gamma , enhanced target cell killing, and improved anti-tumor activity. Additionally, enhanced memory populations arise from CD8 super(+) 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. |
Author | Harrington, Susan M Kwon, Eugene D Gibbons, Rachel M Krco, Christopher J Dong, Haidong Liu, Xin |
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Title | B7-H1 signaling is integrated during CD8 super(+) T cell priming and restrains effector differentiation |
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