Macrophages are key orchestrators of chronic inflammation. They respond to microenvironmental signals with polarized genetic and functional programmes. M1 macrophages which are classically activated by microbial products and interferon-γ, are potent effector cells which kill microorganisms and tumors. In contrast, M2 cells, 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; promote angiogenesis, tissue remodeling and repair. M1 and M2 cells represent simplified extremes of a continuum of functional states. Available information suggests that TAM are a prototypic M2 population. M2 polarization of phagocytes sets these cells in a tissue remodelling, and repair mode. And orchestrate the smouldering and polarized chronic inflammation associated to established neoplasia. Recent studies have begun to address the central issue of the relationship between genetic events causing cancer and activation of pro-tumor inflammatory reactions. Rearrangement of the RET oncogene (RET/PTC) is a frequent, causative and sufficient event in papillary carcinoma of the thyroid. It was recently observed that RET/PTC activates a proinflammatory genetic programme in primary human thyrocytes, including in particular chemokines and chemokine receptors. These molecules are also expressed in vivo and more so in metastatic tumors. These results highlight a direct connection between an early, causative and sufficient oncogene rearrangement and activation of a pro-inflammatory programme in a human tumor. Therapeutic targeting of cancer promoting inflammatory reactions is in its infancy, and its development is crucially dependent on defining the underlying cellular and molecular mechanisms in relevant systems. Chemokines are prime targets for interfering with tumor promotion by inflammatory reactions. Ongoing efforts along this line are encouraging.
|Number of pages||3|
|Issue number||SUPPL. 2|
|Publication status||Published - 2007|
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