Infection, immunoregulation, and cancer

Abstract

As man has moved rapidly from the hunter-gatherer environment to the living conditions of the industrialized countries, the incidences of some cancers have increased alarmingly. Recent increases are usually attributed to dietary changes or to altered exposures to putative carcinogens associated with the modern lifestyle. However, the changes in cancer incidence parallel similar increases in non-neoplastic chronic inflammatory disorders (inflammatory bowel disease, allergies, and autoimmunity), and the epidemiology is often strikingly similar. This parallel is worth exploring, because the increases in chronic inflammatory disorders are at least partly explained by immunoregulatory defects resulting from diminished exposure to microorganisms that co-evolved with mammals and developed a role in driving immunoregulatory circuits (the hygiene hypothesis). Dysregulated chronic inflammation can drive oncogenesis and also provides growth and angiogenic factors that enhance the subsequent proliferation and spread of tumor cells. Thus, a modern failure to downregulate inappropriate inflammation could underlie increases in some cancers in parallel with the increases in chronic inflammatory disorders. This possibility is supported by recent work showing that in some circumstances regulatory T cells protect against cancer, rather than aggravating it, as previously assumed. A greater understanding of these interactions might pave the way to improved microbe-based immunotherapies.

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

“…Although incompletely understood, GI inflammation‐mediated progression to cancer development might involve bacterial toxin production, release of alarmins, gut biofilm modification, dysregulation of gut barrier function, suppression of anti‐inflammatory mediators and transition through an element of high grade dysplasia to cell damage and aneuploidy 13, 19, 35, 40, 60, 61, 62…”

Cholera-Toxin Suppresses Carcinogenesis in a Mouse Model of Inflammation-Driven Sporadic Colon Cancer

“…The long-term consequences of either DSS or CT administration on resident colonic mucosa inflammatory cells, however, did not translate into significant alterations of cytokine gene expression in the colon, which is in line with the subclinical nature of this phenomenon. Nonetheless, these findings support a key role for Tregs in the long-term effects of microbial antigens on mucosal immunity (5,6,8,13).…”

“…Following this reasoning, the use of selected bacterial antigens to modulate cancer-promoting inflammatory events is worth exploring (2,5,6). These products may be a safe and effective approach for reinforcing the regulatory arm of the human immune system.…”

“…Gut microbiota antigenic stimuli play an important role in shaping the intestinal immune responses (4). Therefore, at least in the case of inflammationassociated colon cancer, gut bacteria antigens may influence carcinogenesis (5)(6)(7).…”

8-Nitroguanine, a Potential Biomarker to Evaluate the Risk of Inflammation-Related Carcinogenesis

“…Recently, chronic inflammation induced by infection has been postulated to be an important risk factor of various cancers (Schetter et al, 2010;Aggarwal & Sung, 2011;Kamp et al, 2011;Rook & Dalgleish, 2011;Trinchieri, 2011). Many malignancies arise from areas of infection and inflammation (Balkwill & Mantovani, 2001;Coussens & Werb, 2002).…”