Dynamic Education of Macrophages in Different Area

Authors: Yan Wu Limin Zheng

Publish Date: 2012/06/14

Volume: 5, Issue: 3, Pages: 195-201

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Abstract

Human tumor tissues can often be anatomically classified into areas of cancer nest invading edge and peritumoral stroma each with distinct compositions and functional properties Macrophages Mφ constitute a major component of the leukocyte infiltrate in tumors These cells are derived from circulating monocytes and in response to environmental signals they exhibit distinct phenotypes with diverse functions Soluble factors derived from cancer cells can alter the normal developmental process of Mφ that is intended to trigger transient early activation of monocytes in the peritumoral region which in turn induces formation of suppressive Mφ in cancer nests The activated monocytes in the peritumoral region attenuated the Tcell response by expressing B7H1 and were superior to the suppressive tumor Mφ in inducing Th17 expansion and thus repurpose the inflammatory response away from antitumor immunity the sword and towards tissue remodeling and proangiogenic pathways a plowshare In contrast the suppressive Mφ can induce the production of Tregs in cancer nest Accordingly angiogenesis was most active at the invading edge which was situated close to the peritumoral stroma with activated Mφ and the density of these activated monocytes is selectively associated with vascular invasion and metastasis in patients with hepatocellular carcinoma These data reveal an intriguing mechanism in which human Th17 cells are generated and regulated by a finetuned collaborative action between different types of immune cells in distinct tumor microenvironments These results give important new insights into the distinct role of macrophages in human tumor progression which would be helpful for the rational design of novel immunebased anticancer therapies

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