Biomarker expression for Th17 cells along with tumor progression and lymph node invasion in patients with breast cancer

[ABSTRACT] 【Background】Cancer and inflammation have long been considered two sides of the same coin. With the identification of a subset of CD4(+) T cells that produce interleukin (IL)-17, called Th17 cells, the relationship between this subset and tumor-specific inflammation in the tumor microenvironment has been brought back into the spotlight. The purpose of this study was to determine relationships between Th17 cells and both tumor progression and lymph node invasion, and to evaluate cytokine balance in the tumor microenvironment with tumor progression in patients with breast cancer.【Methods】Tumor tissues and sentinel lymph nodes were collected from 50 breast cancer patients who had been treated at our hospital. Expressions of retinoid orphan nuclear receptor C (RORC), IL-17, IL-21, IL-6, tumor growth factor (TGF)-β, IL-2 and forkhead box P3 (Foxp3) were examined by measuring their mRNA levels with real-time RT-PCR, and correlations of tumor progression to Th17 cells and surrounding cytokines were investigated.【Results】mRNA levels of the RORC gene, which serves as the master gene for Th17, were elevated with increasing clinical stage of breast cancer in both the main tumor and sentinel lymph nodes. In the tumor microenvironment, IL-17 mRNA increased in parallel with RORC expression, while IL-2 mRNA did not increase. TGF-β and IL-6 mRNA levels were elevated with tumor progression, closely correlating with RORC mRNA levels.【Conclusions】Biomarker expression for Th17 cells increased with tumor progression in the tumor microenvironment of human breast cancer. Th17 cells may play a key role in the malignant cycle of tumor progression and tumor-specific inflammation maintenance.