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 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.
Highlights
The leading cause of cancer related mortality is metastatic spread of tumor cells to vital organs
Effective antitumor immunity of peritoneal cavity To investigate the protective antitumor immunity, we immunized mice (10 mice in each group) by the s.c. or i.p. injection of irradiated CT26 colorectal carcinoma or saline alone for 3 times arranged at day 0, 14, and 21, and challenged mice with CT26 cells at day 28 s.c. or i.p., respectively
Cellular immune response in peritoneum induced by the irradiated tumor cells In an attempt to explore the possible mechanism by which the antitumor activity was induced with irradiated tumor cells, we investigated the differences of the immune cell composition in peritoneal that could influence dissemination and metastasis
Summary
The leading cause of cancer related mortality is metastatic spread of tumor cells to vital organs. The peritoneal cavity is proved to be home to a specific type of macrophage (Cailhier et al, 2005; Liu et al, 2006), rich effector memory T lymphocytes (Roberts et al, 2009), a resident population of self-renewing B lymphocytes (Hardy et al, 1994; Paciorkowski et al, 2000), a new subset of tissue-resident NK cells (Gonzaga et al, 2011) and a newly described population found in fat-associated lymphoid clusters (Moro et al, 2010). About the alteration in quantity and function of the resident cell populations to produce autoimmune response for tumor in peritoneum We speculate that these cells form part of the first line of defense against invading pathogens and make peritoneal to be a microenvironment, apart from subcutaneous, which could develop strong autoimmunization response against tumor metastasis in peritoneum and even systemic antitumor effect. These observations may provide a new vaccine strategy for the prevention of peritoneal and systemic metastasis of carcinomas through the induction of the autoimmune response in peritoneum, in addition to subcutaneous immunization
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