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Most pancreatic cancer patients die shortly after being diagnosed, and the disease is difficult to treat.Increasing evidence indicates that the tumor microenvironment surrounding the cancer cells plays an important role in the tumors development and subsequent behavior.This is particularly the case for pancreatic cancer, which is characterized by a dense cancer stroma that contains a rich cellular population;this population includes fibroblasts, endothelial cells,macrophages, and other immune cells.The lack of an effective treatment for pancreatic cancer is largely the result of a lack of understanding of its biologic characteristics and tumorigenesis.Immunotherapy may be a fourth strategy for treating this disease, supplementing surgery, chemotherapy, and radiation therapy.Cellular immunotherapy, which is most often used in cancers for which existing therapies have limited effectiveness, is the administration of specialized cells that kill cancer cells or lead to disease immunity.We have demonstrated that mast cells, a type of immune cell,promote inflammatory progression and immune suppression in PDAC tumorigenesis.Mast cell-targeted therapy resulted in a higher treatment response rate in mouse PDAC than did classic chemotherapy.In addition, tumor cells promote mast cell activation and migration to the tumor site.Because the mast cells activate proliferation of both tumor cells and stellate cells, they potentially contribute to the desmoplastic tumor microenvironment found in PDAC.Therefore, therapy targeting on mast cells may overcome immune suppression and improve PDAC immunotherapy.We will adapt modem immunologic tools to maximize therapeutic response and reduce the deleterious side effects associated with treatment while gaining preclinical and clinical insight into pancreatic cancer immunotherapy, which may finally lead to a new treatment and save patients lives.