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Cancer Lett. 2011 Jun 28;305(2):250-62. doi: 10.1016/j.canlet.2010.10.012. Epub 2010 Nov 18.

Mechanisms linking pathogens-associated inflammation and cancer.

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  • 1DISCAFF, University of Piemonte Orientale A. Avogadro, via Bovio 6, Novara, Italy.

Abstract

It has been estimated that chronic infections with viruses, bacteria and parasites are the causative agents of 8-17% of global cancers burden. Carcinogenesis associated with infections is a complex process, often mediated by chronic inflammatory conditions and accumulating evidence indicate that a smouldering inflammation is a component of the tumor microenvironment and represents the 7th hallmark of cancer. Selected infectious agents promote a cascade of events culminating in chronic inflammatory responses, thus predisposing target tissues to increased cancer susceptibility. A causal link also exists between an inflammatory microenvironment, consisting of inflammatory cells and mediators, and tumor progression. Tumor-Associated Macrophages (TAM) represent the major inflammatory population present in tumors, orchestrating various aspects of cancer, including: diversion and skewing of adaptive responses; cell growth; angiogenesis; matrix deposition and remodelling; construction of a metastatic niche and actual metastasis; response to hormones and chemotherapeutic agents. Recent studies on human and murine tumors indicate that TAM show a remarkable degree of plasticity and functional heterogeneity, during tumour development. In established tumors, TAM acquire an M2 polarized phenotype are engaged in immunosuppression and the promotion of tumor angiogenesis and metastasis. Being a first line of the innate defence mechanisms, macrophages are also equipped with pathogen-recognition receptors, to sense the presence of danger signals, including onco-pathogens. Here we discuss the evidence suggesting a causal relationship between selected infectious agents and the pro-tumoral reprogramming of inflammatory cells, as well as its significance in tumor development. Finally, we discuss the implications of this phenomenon for both cancer prevention and therapy.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

[PubMed - indexed for MEDLINE]
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