B7-H1 signaling is integrated during CD8+ 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 |
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Berlin/Heidelberg
Springer Berlin Heidelberg
01.08.2014
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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 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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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 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. 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. |
Author | Gibbons, Rachel M. Kwon, Eugene D. Liu, Xin Krco, Christopher J. Harrington, Susan M. Dong, Haidong |
AuthorAffiliation | 3 Department of Immunology, College of Medicine, Mayo Clinic, Rochester, USA 2 Department of Urology, College of Medicine, Mayo Clinic, Rochester, USA 1 Biology Discipline, University of Minnesota, Morris, USA |
AuthorAffiliation_xml | – name: 3 Department of Immunology, College of Medicine, Mayo Clinic, Rochester, USA – name: 1 Biology Discipline, University of Minnesota, Morris, USA – name: 2 Department of Urology, College of Medicine, Mayo Clinic, Rochester, USA |
Author_xml | – sequence: 1 givenname: Rachel M. surname: Gibbons fullname: Gibbons, Rachel M. organization: Biology Discipline, University of Minnesota – sequence: 2 givenname: Xin surname: Liu fullname: Liu, Xin organization: Department of Urology, College of Medicine, Mayo Clinic – sequence: 3 givenname: Susan M. surname: Harrington fullname: Harrington, Susan M. organization: Department of Urology, College of Medicine, Mayo Clinic – sequence: 4 givenname: Christopher J. surname: Krco fullname: Krco, Christopher J. organization: Department of Urology, College of Medicine, Mayo Clinic – sequence: 5 givenname: Eugene D. surname: Kwon fullname: Kwon, Eugene D. organization: Department of Urology, College of Medicine, Mayo Clinic, Department of Immunology, College of Medicine, Mayo Clinic – sequence: 6 givenname: Haidong surname: Dong fullname: Dong, Haidong email: Dong.Haidong@mayo.edu organization: Department of Urology, College of Medicine, Mayo Clinic, Department of Immunology, College of Medicine, Mayo Clinic |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/24893858$$D View this record in MEDLINE/PubMed |
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Keywords | Co-stimulatory signaling Effector CD8 Memory CD8 T cell priming T cells |
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SubjectTerms | Animals B7-1 Antigen - immunology B7-H1 Antigen - immunology B7-H1 Antigen - metabolism Cancer Research Cancer Vaccines - immunology CD8-Positive T-Lymphocytes - immunology Cell Differentiation - immunology Cell Proliferation Dendritic Cells - immunology Female Immunology Medicine Medicine & Public Health Mice Mice, Inbred C57BL Oncology Original Article Signal Transduction |
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Title | B7-H1 signaling is integrated during CD8+ T cell priming and restrains effector differentiation |
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