The changes of Th17 cells and the related cytokines in the progression of human colorectal cancers

Background: The role of Th17 cells in colorectal tumorigenesis and development still remains unclear, despite the fact that it has been established in the pathogenesis of autoimmune diseases. Methods: We first analyzed Th17 cells and Treg cells using flow cytometry in the circulation of colorectal adenoma (CRA) and colorectal carcinoma (CRC) patients and healthy controls, and the frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) stimulated by anti-CD3 plus anti-CD28 and treated by IL-1 beta, IL-6, and TGF-beta in different concentrations. We then detected cytokines IL-1 beta, IL-6, IL-17A, IL-21, IL-23 or TGF-beta by ELISA in sera and supernatants from both normal and tumor tissues cultured ex vivo. Results: It was found that the percentage of Th17 and Treg cells increased in the circulation of both CRA and CRC patients; the increase of Th17 cells in the circulation occurred in early stages, whereas the increase of Treg cells in the circulation and the increase of Th17 cells in tumor tissues occurred in advanced stages. The subsequent cytokine profiling showed that, along CRC progression, IL-1 beta, IL-17A and IL-23 underwent a similar change, while IL-6 in CRC exhibited an opposite change, with Th17 cells. In addition, high levels of TGF-beta and IL-17A were detected in tumor tissues rather than in normal mucosa. The in vitro experiment further demonstrated that IL-1 beta, IL-6 or TGF-beta modulated Th17 cell expansion in PBMC. Conclusions: Our study reveals a unique change of Th17 cells, which is regulated possibly by IL-1 beta, IL-6 and TGF-beta in the progression of CRC.