Chronic immune activation and inflammation as the cause of malignancy

Several chronic infections known to be associated with malignancy have esta blished oncogenic properties. However the existence of chronic inflammatory conditions that do not have an established infective cause and are associa ted with the development of tumours strongly suggests that the inflammatory process itself provides the prerequisite environment for the development o f malignancy. This environment includes upregulation of mediators of the in flammatory response such as cyclo-oxygenase (COX)-2 leading to the producti on of inflammatory cytokines and prostaglandins which themselves may suppre ss cell mediated immune responses and promote angiogenesis. These factors m ay also impact on cell growth and survival signalling pathways resulting in induction of cell proliferation and inhibition of apoptosis. Furthermore, chronic inflammation may lead to the production of reactive oxygen species and metabolites such as malondialdehyde within the affected cells that may in turn induce DNA damage and mutations and, as a result, be carcinogenic. Here it is proposed that the conditions provided by a chronic inflammatory environment are so essential for the progression of the neoplastic process that therapeutic intervention aimed at inhibiting inflammation, reducing an giogenesis and stimulating cell mediated immune responses may have a major role in reducing the incidence of common cancers. (C) 2001 Cancer Research Campaign.