Implications of anti-cytokine therapy in colorectal cancer and autoimmune diseases.

Abstract

Up to 20% of all cancers have been linked to chronic inflammation and persistent infections. However, almost all solid tumours contain immune infiltrates, and tumour-associated inflammatory cells play broad roles in different stages of tumour development and malignant progression. Cytokines are important mediators of the inflammatory effect on tumorigenesis both in inflammation-induced cancer and in the inflammation that follows tumour development. We have shown interleukin (IL)-6 to be an important tumour promoter in early colitis-associated cancer (CAC). IL-6 is mainly produced by tumour-infiltrating myeloid cells under the control of NF-κB. IL-6 promotes proliferation of tumour-initiating cells derived from the intestinal epithelium and protects them from apoptotic elimination. These pro-survival and proliferative effects of IL-6 are mainly mediated by STAT3, whose ablation in intestinal epithelial cells significantly reduces CAC tumorigenesis. More recently, we found a critical role for IL-23 and its downstream cytokines IL-17 and IL-22 in the development of CAC. These findings suggest that such cytokines or the cells that produce them may provide new therapeutic or preventive targets in forms of colorectal cancer that are linked to inflammation.