Intestinal microbiota alters omental tumor growth

The omentum is an adipose tissue that contains milky spots (MS). The MS are similar to secondary lymphoid organs and can generate B and T cell immune responses to peritoneal antigens. Additionally, omentum CD4 + CD25 + FoxP3 + T regulatory cells (Tregs) display an activated phenotype CD44 hi CD62L low . Moreover, the omentum also collects metastasizing tumor cells in the peritoneal cavity and tumors growing in the omentum are associated with poor clinical prognosis. Here we show that intestinal microbiota affects Tregs activation profile and impairs tumor growth in omentum. Our transplantable tumor model in wild type (WT) mice shows that peritoneal tumors grow progressively in the omentum and peritoneal cavity in WT mice, whereas in germ free (GF) mice tumors do not grow. Omental tumor growth in WT mice is associated with an increase in PD-1 + Tregs, while tumor-specific CD8 + T are reduced. However, in GF mice numbers of PD1 + Tregs remain unaltered but tumor specific CD8 + T cells are still present. After co-housed GF mice with WT mice, ex-GF mice showed tumor growth and restore the increase in PD-1 + Tregs with low number of specific CD8 + T cells. The induction of tolerance requires PD-1 + Tregs. These data suggest that intestinal microbiota has a role in omental Tr activation and in the tolerance to peritoneal tumors.