IL-1ß/IL-6 network in the tumor microenvironment of human colorectal cancer.

OBJECTIVES: Recent studies suggest that the interaction between interleukin (IL)-1ß and IL-6 in the microenvironment might be involved in the development and progression of human colorectal cancer (CRC). However, the expression of IL-1ß/IL-6 network within the CRC microenvironment is not fully understood. MATERIALS AND METHODS: The level of IL-1ß/IL-6 network expression in 40 biopsies of sporadic CRC and 15 biopsies of controls was assessed using quantitative real-time polymerase chain reaction (PCR) assay, immunohistochemistry (IHC) and double immunofluorescence staining. RESULTS: Quantitative results obtained by real-time PCR revealed that both IL-1ß and IL-6 mRNA expressions were increased in CRC tissues compared with expressions in controls. In which, IL-6 mRNA expression in primary CRC tissues showed a statistically significant relationship with tumor invasion depth. IHC observations confirmed that increased expression of IL-1ß and IL-6 immunoreactivities was located in both the CRC epithelium and stroma. Furthermore, IHC results also revealed that increased expression of IL-1ß receptor type 1 (IL-1R1) and IL-6 receptor (IL-6R) were observed in both CRC epithelial and stromal cells. IHCs in serial CRC sections and double immunofluorescence staining revealed a highly co-expression of IL-1R1 immunoreactivity with IL-6 immunoreactivity in the same cells, which confirmed a histological fundament of IL-1ß/IL-6 network. CONCLUSION: The IL-1ß/IL-6 network is highly expressed in the CRC microenvironment, indicating that this network is important in the progression of CRC.

Tumor-Associated Fibroblasts and Microvessels Contribute to the Expression of Immunosuppressive Factor Indoleamine 2, 3-Dioxygenase in Human Esophageal Cancers.

Recent studies have provided considerable evidence to support the hypothesis that tumor stroma plays a crucial role in the induction of immune tolerance to human cancers. Here, we investigated the contribution of reactive stromal tumor-associated fibroblasts (TAFs) and microvessels to the immunosuppressive factor indoleamine 2,3-dioxygenase (IDO) expression in the ESCC microenvironment. The immunohistochemical (IHC) analyses demonstrated a significant increased densities of TAFs and microvessels in the ESCC stroma, double IHCs showed that these increased TAFs and microvessels were with a high proliferation activity. Further IHC examinations revealed that increased expression of IDO were frequently observed in the stromal cells with TAF morphology and microvessels. Double immunofluorescence examinations confirmed the colocalization of IDO positive cells with SMA-alpha positive TAFs and CD34 positive endothelial cells in the ESCC stroma. Our current findings strongly suggest that the activated stromal TAFs and endothelial cells of microvessels contribute to the expression of IDO and then the orchestration of immunosuppressive microenvironment.