In a recent review article in Cancer and Metastasis Reviews Leena von Hertzen, H. Joensuu and T. Haahtela, from the Skin and Allergy Hospital, Helsinki University Central Hospital, Finland, summarize the epidemiological data related to microbial deprivation and cancer, and discuss the involvement of the T helper (Th)17/Interleukin(IL)-23 axis and the immunomodulatory potential of environmental microbiota in cancer-associated inflammation.
The cancer-inflammation link was probably first recognized by Virchow in the 1860s, and nowadays it is well accepted concept that inflammatory responses play decisive roles at different stages of tumor development.
Inflammation has been suggested to increase the risk for cancer, but microbial components may play an important role in endorsing the innate immunity and regulatory networks and might thus prevent persistent inflammation and further carcinogenesis.
Recent evidence indicates that people who live in microbe-rich environments in simple living conditions are relatively protected against asthma, allergies and some autoimmune diseases. Micro-organisms that co-evolved with man since ancient times generally do not elicit overt immune responses but rather trigger the immune regulatory network to induce regulatory cytokines.
Thus, hypothetically, cancers might occur less frequently in populations that are heavily exposed to environmental microbiota due to well functioning immunosurveillance. In fact, recent occupational studies report reduced cancer rates among populations presumably heavily exposed to environmental microbiota.
In Cancer and Metastasis Reviews L. von Hertzen, H. Joensuu and T. Haahtela discuss that Th1 immunity has traditionally been considered an important defense mechanism in immunosurveillance related to tumor development and progression. New studies however indicate that inflammation exerted by the Th17/IL-23 axis is associated with tumor progression.
The authors of this review suggest that continuous microbial exposure may be associated with 1) activation of microbial receptors on/in immune and other cells, which may have direct antitumor effect and an indirect effect by endorsing innate immunity and homeostatic mechanisms, and 2) strengthening of the regulatory network, which in turn can prevent or dampen in early phases the development of Th17 cells and inflammatory mediators, such as Cox-2 and PGE2, central to cancer-promoting inflammation. This new concept might pave a way for novel strategies for cancer prevention and therapy.