Chronic inflammation and the development of malignancy in the GI tract

The role of immunologic factors in the development of gastrointestinal (GI) neoplasia, made evident from the high degree of association of chronic intestinal or gastric inflammation with the development of cancer, has attracted much attention because it promises new ways of treating disease. Here we develop the idea that immunologic factors influence the appearance of GI cancer on two levels: (i) a basic and initiating level during which the epithelial cell is induced to undergo pre-cancerous molecular changes that render it prone to further cancer progression; and (ii) a secondary level that builds on this vulnerability and drives the cell into frank malignancy. This secondary level is uniquely dependent on a single epithelial cell signaling pathway centered on STAT3, and it is this pathway upon which stimulation of mucosal cytokine production and microbiota effects converge.