Whole genome expression analysis of tumor regulatory T cells expressing interleukin-10. Mus musculus

The tumor microenvironment contains high frequencies of inflammatory regulatory T (Treg) cells. These Treg exhibit superior regulatory function compared with those from other environments such as the spleen, partially due to expression of anti-inflammatory interleukin-10. In order to gain insight into the origins and functional roles of different Treg subsets, we used whole genome microarray analysis to characterize tumor IL-10+ and tumor IL-10- Treg subsets obtained from VERT-X reporter mice bearing transplantable tumors, along with total tumor Treg and spleen Treg from FoxP3-EGFP reporter mice. Few genes were found to differ between IL-10+ and IL-10- tumor Treg subsets (29 upregulated, 88 downregulated), suggesting a common origin of each Treg subset. The specific gene expression profile of IL-10+ tumor Treg was associated with the tumor microenvironment and absent from spleen Treg, suggesting it to be driven by components of the inflammatory tumor microenvironment. The IL-10+ tumor Treg gene expression profile displayed upregulation of genes associated with a higher activation state and greater effector function. Overall design: Pooled MC38 tumor tissue from VERT-X or FoxP3-EGFP reporter mice were used to obtain IL10+ tumor Treg (VERT-X), IL10- tumor Treg (VERT-X) and total tumor Treg (FoxP3-EGFP). Spleens from tumor-free FoxP3-EGFP mice were used for spleen Treg. Three experiments for each population gave a total 12 RNA samples.