B7-H1 signaling is integrated during CD8 super(+) 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: 01.08.2014
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-014-1563-6

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.