Implications for Tumor Microenvironment and Epithelial Crosstalk in the Management of Gastrointestinal Cancers

Figure 1

Inflammation and tissue restitution have complex implications for the gastrointestinal microenvironment. (a) The GI epithelium is exposed to a variety of inflammatory agents including bacteria, viruses, parasites, chemicals, and other components which promote injurious shifts in microbial populations and/or directly and (b) induce reactive oxygen and nitrogen species leading to epithelial DNA damage and mutations. Following DNA damage, (c) certain cell types escape DNA repair mechanisms, maintaining these somatic mutations (red), while (d) other cells with effectual DNA repair mechanisms, undergo apoptosis. (e) Macrophages (pink) recruited to the site of injury can engulf pathogens, as well as apoptotic epithelial cell bodies destroyed during inflammation. Macrophage-based detection of signal combinations indicating successful clearance of pathogens (e.g., IL-4 + apoptotic phosphatidyl-serine functional group) can induce (f) macrophage polarization and alternative activation and subsequent anti-inflammatory signaling. (g) Exposure to this signaling may promote tumorigenesis and/or progression in susceptible epithelial cells harboring mutations C or other sources, leading to establishment of tumors and/or metastatic transformation.