WORMTUMORS · Worm power: Can helminths modify the development of colorectal cancer?

Worm power: Can helminths modify the development of colorectal cancer?

Colorectal cancer (CRC) causes ~694,000 deaths a year and is the 3rd most prevalent cancer in the world. Currently, the incidence of CRC is predicted to increase significantly more in low- and middle-income countries (LMIC) than in high-income countries (HIC) by 2035. In LMIC, infectious disease, including helminth infection, contribute to a third of all cancer cases and 20% of cancer deaths. Helminth infection affects more than 1.5 billion people in LMIC and can protect against immune-mediated diseases, in fact, live infection or helminth products are being used within clinical trials as novel therapeutics to treat inflammatory bowel disease. As LMIC develop economically, exposure to dietary and lifestyle risk factors associated with cancer will collide with existing high rates of infection with pathogens such as helminths. In this scenario, the ability of helminths to subvert or suppress the immune system of the host may be detrimental to cancer development. Currently it is unknown how helminth modulation of immunity influences CRC. The overriding objective of this proposal therefore, is to determine how helminth exposure influences colorectal cancer development. We have found that helminth infection increases inflammation and tumor development in a mouse model of disease. Changes in diet to one rich in fatty acids consumed in HIC also increased disease. Diet change clashed with underlying helminth infection resulting in a very poor outcome in this model. Increases in colorectal cancer following helminth infection and diet change are reliant on live helminth infection and are regulated by IL-4Ra signalling. Increased tumour development is associated with a reduced anti-tumor response and the increased production of inflammatory lipid mediators in the colon, where administration of one mediator increased tumor formation in naive mice. We conclude that helminth infection and diet change exacerbate colorectal cancer through regulation of fatty acid metabolism and increased production of lipid inflammatory mediators.

Data: CORDIS, © European Union