Molecular links between inflammation

Already in the nineteenth century it was realized that cancer was linked to inflammation. This perception has essentially disappeared for a long time. The inflammation–cancer connection is now part of an accepted paradigm based on different lines of work and leading to a generally accepted paradigm (Balkwill and Mantovani, 2001; Coussens and Werb, 2002; Balkwill et al., 2005; Mantovani et al., 2008) (Figure 17.1). Chronic inflammation predisposes to different forms of cancer. The triggers of chronic inflammation, which increase cancer risk, include microbial infections (e.g., H.pilori for gastric cancer and mucosal lymphoma), autoimmune diseases (e.g., inflammatory bowel disease for colon cancer), and inflammatory conditions of uncertain origin (e.g., prostatitis for prostate cancer). Usage of non-steroidal anti-inflammatory agents is associated with protection against various tumors, a finding that to a large extent mirrors that of inflammation as a risk factor for certain cancers. The “inflammation–cancer” connection is not restricted to increased risk for a subset of tumors. An inflammatory component is present in the microenvironment of most neoplastic tissues, including those not causally related to an obvious inflammatory process. Key features of cancer-related inflammation include the infiltration of white blood cells, prominently tumor associated macrophages (TAM); the presence of polipeptide messengers of inflammation (cytokines such as tumor necrosis factor (TNF) or interleukin-1 (IL-1) and chemokines such as CCL2); the occurrence of tissue remodelling and angiogenesis.