Microbial deprivation, inflammation and cancer

Abstract

Dysregulated immune function is involved in the pathogenesis of many common human diseases. Living in urban, microbe-poor environment may have a profound influence on the immune function and eventually also on carcinogenesis. Unfortunately, few studies have thus far addressed the role of exposure to the environmental microbiota on the risk of cancer. Which mechanisms are broken in individuals prone to develop chronic inflammation in response to exposure that does not cause harm in others? Recent work in immunology has revealed that Th17 cells, a third subset of Th cells, and inflammatory cytokines, particularly IL-23, are closely linked with tumour-associated inflammation. Albeit the precise role of Th17 cells in cancer is still unclear and a matter of debate, accumulating evidence shows that Th17 cells are enriched in a wide range of human tumours, and that these tumour-derived Th17 cells may promote angiogenesis, tumour growth and inflammation. Regulatory T cells, in turn, appear to have counter-regulatory effects on Th17 cells and can inhibit their function. Thus, the regulatory network, induced and strengthened by continuous exposure to environmental microbiota, may play an important role in tumour immunobiology in preventing the establishment of chronic inflammation in its early phases. In addition, the discovery of the Toll-like receptor (TLR) system has brought micro-organisms to new light; continuous signalling via these TLRs and other receptors that sense microbial components is necessary for epithelial cell integrity, tissue repair, and recovery from injury. In this communication, we summarise the epidemiological data of living in environments with diverse microbial exposures and the risk of cancer, and discuss the related immunological mechanisms, focusing on the links between environmental microbiota, the Th17/IL-23 axis and cancer-associated inflammation.

Environmental Changes, Microbiota, and Allergic Diseases

“…The development and maintenance of epithelial-cell integrity, tolerance, and tissue repair requires the interaction with microbes and immune cells via their specific receptors. When these microbial stimuli are absent, it cannot adequately induce the immunoregulatory circuits including regulatory dendritic cells, regulatory T (Treg) cells and regulatory cytokines such as IL-10, transforming growth factor-β (TGF-β) 46. Interestingly, it has also been shown that an inflammatory milieu enhances the conversion of Treg cells to inflammatory Th17 cells and enriches the bacteria that tolerate to the inflammatory mediators in microbiota, thereby creating a self-perpetuating system.…”

Pelvic inflammatory disease increases the risk of a second primary malignancy in patients with cervical cancer treated by surgery alone

“…Chronic inflammation or infection could contribute to the development or activation of malignant disease. [18,19] PID might constitute a marker for gynecological cancers that could enable early treatment and improved prognosis.…”

Mesenchymal Stem Cells as Vehicles for Targeted Therapies

“…Dvorak actually described the tumor as an unhealed wound that produces a continuous source of inflammatory mediators (Dvorak, 1986). Inflammation is a component present during all steps of tumor development and in all types of tumors (Sansone & Bromberg, 2011;Spaeth et al, 2008;von Hertzen et al, 2011;Wallace et al, 2010). The migration of MSCs to tumors is well documented (Loebinger et al, 2009a(Loebinger et al, , 2009bNakamizo et al, 2005;Studeny et al, 2002Studeny et al, , 2004Xin et al, 2007).…”