Combination therapy with dendritic cell based vaccination and myeloid derived suppressor cell depletion augments immunity in a murine pancreatic carcinoma model (66.8)

Abstract

Abstract Pancreatic cancer is an aggressive disease with poor prognosis. Immunotherapy may be less effective in treating pancreatic tumors due to suppression by myeloid derived suppressor cells (MDSC). In this study, we sought to determine the effect of combining MDSC depletion with dendritic cell (DC) vaccination in a murine model of pancreatic cancer. In mice, MDSC are characterized by surface expression of CD11b and Gr-1. After injection of Panc02 tumor cells, a higher percentage (29.2%) of MDSC were present in spleens of tumor-bearing mice as compared to naïve mice (6.38%, p<0.05). MDSC isolated from tumor-bearing mice significantly suppressed proliferation of antigen stimulated T cells. It has been reported that Gemcitabine (Gem), a chemotherapeutic drug, can selectively target MDSC. Flow cytometry results showed a decrease in the percentage of MDSC in splenocytes from Gem-treated tumor-bearing (6.57%) compared to untreated mice (24.3%, p<0.01). To study the effects of DC vaccination combined with MDSC depletion on tumor rejection, mice received PANC02 tumor cells and were treated with 3 injections of DC at 3-4 day intervals. After the final vaccination, mice received Gem. Survival was measured in 50% of mice receiving both DC vaccination and Gem (p<0.05 as compared to each treatment alone). Results from this study suggest that the depletion of MDSC enhances DC induced immunity in a murine model and raises the potential for this strategy in patients with pancreatic cancer.