Total body irradiation has been shown to enhance the efficacy of adoptively transferred tumor cells. The mechanisms responsible for this have largely been attributed to removal of cytokine sinks, suppressive cells and increase in danger signals. We now show that irradiation results in the down regulation of the macrophage scavenger receptor 1 on dendritic cells within the tumor and as a consequence reduces lipid uptake by tumor resident dendritic cells. The tumor antigen targeted in our model is Mammaglobin-A, expressed by approximately 80% of human breast tumors. We show that only the adoptive transfer of Mammaglobin-A2.4 specific CD8 T cells leads to long-term tumor regression and in combination with low-dose irradiation prevents tumors from reoccurring. These data demonstrate that irradiation reduces lipid uptake by dendritic cells and increases the efficacy of adoptively transferred Mammaglobin-A specific CD8 T cells providing a potential therapy for the treatment and/or prevention of breast cancer.
- Copyright © 2011 by The American Association of Immunologists, Inc.