B7-H1 signaling is integrated during CD8+ T cell priming and restrains effector differentiation

• Published in: Cancer Immunology, Immunotherapy Vol. 63; no. 8; pp. 859 - 867
• Main Authors: Gibbons, Rachel M., Liu, Xin, Harrington, Susan M., Krco, Christopher J., Kwon, Eugene D., Dong, Haidong
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2014
• Subjects: 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; Co-stimulatory signaling; Effector CD8; Memory CD8; T cell priming; T cells
• DOI: 10.1007/s00262-014-1563-6
• ISSN: 0340-7004

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.