Chemoimmunotherapy provides protective immunity of murine pancreatic cancer model (P2070)

Abstract

Abstract Pancreatic cancer is an aggressive disease with grim prognosis. Immunotherapy is less effective in treating tumors partly due to Myeloid Derived Suppressor Cells (MDSC). In this study we evaluated tumor regression due to MDSC depletion with dendritic cell (DC) vaccination of pancreatic tumor bearing (TB) mice. Flow cytometry results showed a significant increase in the percentage of MDSC in tumors and spleens of TB mice compared to naïve mice. MDSC isolated from TB mice significantly suppressed antigen-specific T cell responses compared to naive mice. Gemcitabine (GM) is a chemotherapeutic drug for cancer therapy. Flow cytometry results showed a significant decrease in the percentage of MDSC in splenocytes from GM-treated TB and naïve mice. To study effects of DC vaccination combined with MDSC depletion on tumor rejection, mice were vaccinated with PANC02 lysate-pulsed DC or PBS, three times at seven-day intervals. One week after final vaccination, mice were challenged with PANC02 tumor cells. Mice in the vaccinated and control groups either received PBS or GM therapy. In vivo depletion of MDSC was performed three days prior to tumor challenge, continued until the end of the experiment and was confirmed using flow cytometry. A significant survival benefit was seen in mice receiving both DC vaccination and MDSC depletion. Results from this study strongly suggest that the depletion of MDSC significantly enhances protective immunity in a murine pancreatic cancer model.