B7-H1 negatively regulates IL-12 production by dendritic cells (165.10)

Abstract

Abstract A promising strategy in tumor immunotherapy is the use of activated dendritic cells as vehicles for tumor vaccines. Clinical trials of dendritic cell-based immunotherapies have proven successful, resulting in recent FDA approval for their use in the treatment of late-stage prostate cancer. Current formulations for dendritic cell-based immunotherapies are capable of prolonging patient survival by only four months, providing motivation for further investigation of ways to enhance dendritic cell priming of anti-tumor T cell responses. Since the discovery of B7-H1 by our laboratory, we have been investigating the regulatory function of B7-H1 expressed by immune cells. In preliminary studies investigating the use of B7-H1 knockout dendritic cells as tumor vaccines, we found that B7-H1 knockout dendritic cells prime enhanced anti-tumor CD8 T cell responses. Further investigations revealed that the enhanced CD8 T cell response raised by B7-H1 knockout dendritic cells is not due to a lack of signaling through the receptors for B7-H1 on CD8 T cells. We observed that B7-H1 knockout dendritic cells produced increased levels of IL-12, a key cytokine that is centrally involved in both innate and adaptive immunity. Our results suggest that B7-H1 expressed by dendritic cells has a role in negatively regulating IL-12 production, and as a result B7-H1 deficient dendritic cells are able to prime enhanced anti-tumor CD8 T cell responses.