Links between cancer and inflammation were first made in the nineteenth century, on the basis of observations that tumours often arose at sites of chronic inflammation and that inflammatory cells were present in biopsied samples from tumours 1 . The idea that these processes are connected was out of favour for more than a century, but there has been a recent resurgence in interest. Several lines of evidence 1-4 (Box 1) -based on a range of findings, from epidemiological studies of patients to molecular studies of genetically modified mice -have led to a general acceptance that inflammation and cancer are linked.Epidemiological studies have shown that chronic inflammation predisposes individuals to various types of cancer. It is estimated that underlying infections and inflammatory responses are linked to 15-20% of all deaths from cancer worldwide 1 . There are many triggers of chronic inflammation that increase the risk of developing cancer. Such triggers include microbial infections (for example, infection with Helicobacter pylori is associated with gastric cancer and gastric mucosal lymphoma), autoimmune diseases (for example, inflammatory bowel disease is associated with colon cancer) and inflammatory conditions of unknown origin (for example, prostatitis is associated with prostate cancer). Accordingly, treatment with non-steroidal anti-inflammatory agents decreases the incidence of, and the mortality that results from, several tumour types [5][6][7] .The hallmarks of cancer-related inflammation include the presence of inflammatory cells and inflammatory mediators (for example, chemokines, cytokines and prostaglandins) in tumour tissues, tissue remodelling and angiogenesis similar to that seen in chronic inflammatory responses, and tissue repair. These signs of 'smouldering' inflammation 2 are also present in tumours for which a firm causal relationship to inflammation has not been established (for example, breast tumours). Indeed, inflammatory cells and mediators are present in the microenvironment of most, if not all, tumours, irrespective of the trigger for development.Studies of genetically modified mice, adoptive-transfer experiments in mice, and analyses of human tumours have allowed researchers to begin to unravel the molecular pathways that link inflammation and cancer. Here we review current knowledge of the molecular and cellular pathways that link inflammation and cancer, and we describe how these pathways suppress effective antitumour immunity during tumour progression. We also discuss how cancer-related inflammation affects many aspects of malignancy, including the proliferation and survival of malignant cells, angiogenesis (which is required for the survival of cells within tumours of a certain size), tumour metastasis, and tumour response to chemotherapeutic drugs and hormones.Advances in understanding the genetic pathways involved in cancer have led to the development of a range of therapies that target malignant cells. Understanding the pathways involved in cancer-related inflammation could ...

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Triggering of innate immunity and mounting of an acute response is generally followed by a late phase where regulatory mechanisms, tissue repair, and remodeling prevail. Acute inflammation triggered by exogenous administration of TNF-α, IL-1, and LPS has been known under certain conditions to promote malignancy and metastasis (Balkwill and Mantovani, 2001). However, chronic local inflammatory reactions with little systemic manifestations are more relevant to the pathophysiology of most neoplastic conditions.The diversity of inflammatory reactions is dictated by the primary stimulus as well as by exogenous and endogenous modifying signals. At one end of the spectrum, type 1 inflammation, typified by granuloma formation, is elicited by intracellular pathogens. At the other extreme, inflammatory reactions to parasites are characterized by eosinophil and mast cell/basophil infiltration and by extensive tissue remodeling (type 2 inflammation).Macrophages are key cells in chronic inflammation. They respond to microenvironmental signals with polarized genetic and functional programs (Gordon, 2003;Mantovani et al., 2002). M1 macrophages are involved in Type 1 reactions and are classically activated by microbial products, killing microorganisms and producing reactive oxygen and nitrogen intermediates. In contrast, M2 cells, involved in Type 2 reactions (Mantovani et al., 2004b;Mantovani et al., 2002), tune inflammation and adaptive immunity, promote cell proliferation by producing growth factors and products of the arginase pathway (ornithine and polyamines), scavenge debris by expressing scavenger receptors, and promote angiogenesis, tissue remodeling, and repair. M1 and M2 cells are extremes in a continuum

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