Cancer: A Tale of Aberrant PRR Response

Cancer is a disease of complex etiology and multistep progression, manipulating the regular routes to homeostasis. Any deviation from homeostasis alerts the innate immune system and provokes inflammation. Inflammation is generated by the signaling cascades launched by the pattern recognition receptors (PRRs), the germ-line encoded molecules dedicated to sense pathogen, or danger-associated molecular patterns (PAMPs or DAMPs) in case of pathogen/foreign matter invasion and intrinsic disturbances, respectively (1–3). Through inflammation, PRRs eliminate stress signals and re-establish homeostasis in the body, via drawing the required cellular machinery to the inflammatory sites. However, the same lympho-reticular infiltrate has been linked with incidence of cancer at the site of chronic inflammation, since 1863, by Rudolf Virchow (4). From 1990s vast amount of literature has accumulated associating soluble and cellular factors of innate immune system with prevalence and progression of cancer. Furthermore, in the past decade, several pathogens have been linked with cancer as well [Ref. (5, 6) and references therein]. Fascinatingly, it is remarkable how the tightly regulated sensory system for stress removal and maintenance of homeostasis functions anomalously and promotes occurrence and progression of cancers (7–9).