Effective response of the peritoneum microenvironment to peritoneal and systemic metastasis from colorectal carcinoma.

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 peritoneal carcinomatosis 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 the peritoneal cavity, were revealed to have significant differences between immunized and non-immunized mice and these contributed to antitumor responses. We also observed that both serum and peritoneal lavage fluid harvested from immunized mice showed the presence of CT26-specific autoantibodies. In addition, increase in level of TGF-β1 and IL-10 in serum but a decrease of TGF-β1 in peritoneum was found. Taken together, these findings may provide a new vaccine strategy for the prevention of peritoneal and even systemic metastasis of carcinomas through induction of an autoimmune response in the peritoneum.