Effective Response of the Peritoneum Microenvironment to Peritoneal and Systemic Metastasis from Colorectal Carcinoma

Abstract

We here document discovery of a new and simple model of tumor seeding involving the mouse peritoneum.Irradiated tumor cells administered by i.p. injection provided effective vaccination against peritonealcarcinomatosis and distal metastasis with colorectal carcinomas. In flow cytometric analysis, CD4+ and CD8+T lymphocytes, macrophages and myeloid-derived suppressor cells (MDSCs), which are easy to obtain in theperitoneal cavity, were revealed to have significant differences between immunized and non-immunized miceand these contributed to antitumor responses. We also observed that both serum and peritoneal lavage fluidharvested from immunized mice showed the presence of CT26-specific autoantibodies. In addition, increase inlevel of TGF-β1 and IL-10 in serum but a decrease of TGF-β1 in peritoneum was found. Taken together, thesefindings may provide a new vaccine strategy for the prevention of peritoneal and even systemic metastasis ofcarcinomas through induction of an autoimmune response in the peritoneum.