Accumulation of FoxP3+ T regulatory cells in the tumor microenvironment of human colorectal adenomas.

Objectives: T regulatory cells (Tregs) play a critical important role for the occurrence and development of human tumors. Most human colorectal cancers (CRCs) develop from the preformed adenomas, this study is therefore designed to evaluate forkhead box P3 (FoxP3)+ Tregs in human colorectal adenomas.

Materials And Methods: FoxP3+ Tregs in human colorectal adenomas were evaluated with immunohistochemistry (IHC) and real-time PCR, and compared to CRCs and normal tissues. In addition, the change of Treg immunosuppressive cytokine interleukin (IL)-10 was examined with IHC and real-time PCR.

Results: increased FoxP3+Tregs were observed in the adenomatous stroma/epithelium and the density in colorectal adenomas, which was similar to that in the CRCs, significantly increased as compared to normal tissues. Numerous IL-10+cells were observed in the adenomatous stroma, but not in adenomatous epithelium, as compared with the controls. The density grading score of IL-10+ cells in the adenomas confirmed an increased density of IL-10+cells in the adenomatous/CRC stroma. Double IHCs with CD4/CD25 and IL-10/FoxP3 antibodies confirmed above observations and revealed that IL-10 was at least partially released from increased Tregs. Quantitative real-time PCR results confirmed that the expression levels of FoxP3 and IL-10 mRNAs in the adenomas were increased, which equivalent to that in the CRCs.

Conclusion: accumulation of FoxP3+ Tregs in the tumor microenvironment is an early event along the adenoma-carcinoma sequence, and might play a role in the regulation of host immune response to the initiation of CRC.