NDLI: Dynamic Education of Macrophages in Different Areas of Human Tumors

Content Provider	Springer Nature Link
Author	Wu, Yan Zheng, Limin
Copyright Year	2012
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 T-cell response by expressing B7-H1, and were superior to the suppressive tumor Mφ in inducing Th17 expansion, and thus repurpose the inflammatory response away from anti-tumor 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 fine-tuned 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 immune-based anticancer therapies.
Starting Page	195
Ending Page	201
Page Count	7
File Format	PDF
ISSN	18752292
Journal	Cancer Microenvironment
Volume Number	5
Issue Number	3
e-ISSN	18752284
Language	English
Publisher	Springer Netherlands
Publisher Date	2012-06-14
Publisher Institution	International Cancer Microenvironment Society
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Macrophages (Mφ) Microenvironment Hepatocellular carcinoma (HCC) Inflammation Immune-editing Oncology Cell Biology Biomedicine general Biochemistry Immunology Cancer Research
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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