Pancreatic Stellate Cells Promote Tumor Progression by Promoting an Immunosuppressive Microenvironment in Murine Models of Pancreatic Cancer

Abstract

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer with poor prognosis. Pancreatic stellate cells (PSCs) play a vital role in PDAC development. The aim of this study was to explore tumor microenvironment response to PSCs in an orthotopic pancreatic cancer mouse model and to assess if PSCs secreted factors that can facilitate an immunosuppressive microenvironment. METHODS: Pancreatic ductal adenocarcinoma orthotopic tumor model, derived from coinjection of Panc02 cells plus PSCs, was used to investigate tumor proliferation, metastasis, and the population of immune cells in vivo, including regulatory T cells, M2-type macrophages, myeloid-derived suppressor cells, CD8 T cells, CD4 T cells, M1-type macrophages, natural killer (NK), and NK T cells. RESULTS: Pancreatic stellate cells promoted PDAC growth not only induced cell proliferation and metastasis, but also significantly increased the suppressive immune cell population of regulatory T cells, M2-type macrophages, and myeloid-derived suppressor cells. In addition, PSCs decreased the immune cell population of CD8 T, CD4 T cells, and M1-type macrophages in the spleen and tumor tissues of the tumor-bearing mice. Moreover, PSCs decreased the population of NK and NK T cells in the tumor tissues. CONCLUSIONS: Our findings support PSCs playing multiple roles in PDAC development via promoting immunosuppressive microenvironment.