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

Jiansheng Wang,Guosheng Feng,Kaiyu Xu,Yuchen Li,Bao-Zhu Yuan,Hong Gao,Jing Wu,Chenghua Luo,Xuebin Wu

doi:10.1186/1471-2407-12-418

Abstract

BackgroundThe 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.MethodsWe 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-1β, IL-6, and TGF-β in different concentrations. We then detected cytokines IL-1β, IL-6, IL-17A, IL-21, IL-23 or TGF-β by ELISA in sera and supernatants from both normal and tumor tissues cultured ex vivo.ResultsIt 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-1β, 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-β and IL-17A were detected in tumor tissues rather than in normal mucosa. The in vitro experiment further demonstrated that IL-1β, IL-6 or TGF-β modulated Th17 cell expansion in PBMC.ConclusionsOur study reveals a unique change of Th17 cells, which is regulated possibly by IL-1β, IL-6 and TGF-β in the progression of CRC.

Highlights

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
Percentage of the circulating Th17 cells in colorectal adenoma (CRA) and Colorectal cancer (CRC) patients To investigate the changes of Th17 cells in the progression of CRC, we first measured Th17 cells in the peripheral blood mononuclear cells (PBMCs) of CRA and CRC patients and healthy controls
The percentage of Th17 cells was significantly increased in both CRA and CRC patients (1.7%; 1.3% to 2.4%; P < 0.001) as compared with healthy controls (0.7%; 0.4% to 1.2%)

Summary

Introduction

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. Among different T lymphocyte subpopulations, CD4+CD25+ T cells (Tregs) are vital in maintaining immune tolerance and homeostasis. They may promote tumor progression by inhibiting anti-cancer immune responses [12,13]. The Th17 cell, which is another CD4-positive T lymphocyte subpopulation with its designation following the feature of secreting IL-17, has been extensively described for its involvement in several autoimmune diseases and chronic inflammatory syndromes [16,17]. The role of Th17 cells in tumor immunity was less studied as compared with Treg cells

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