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Cancer Cell. 2009 Sep 8;16(3):183-94. doi: 10.1016/j.ccr.2009.06.017.

Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus "N2" TAN.

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  • 1Thoracic Oncology Research Laboratory, 1016B ARC, University of Pennsylvania, Philadelphia, PA 19104-6160, USA. fridlender@hadassah.org.il

Abstract

TGF-beta blockade significantly slows tumor growth through many mechanisms, including activation of CD8(+) T cells and macrophages. Here, we show that TGF-beta blockade also increases neutrophil-attracting chemokines, resulting in an influx of CD11b(+)/Ly6G(+) tumor-associated neutrophils (TANs) that are hypersegmented, more cytotoxic to tumor cells, and express higher levels of proinflammatory cytokines. Accordingly, following TGF-beta blockade, depletion of these neutrophils significantly blunts antitumor effects of treatment and reduces CD8(+) T cell activation. In contrast, in control tumors, neutrophil depletion decreases tumor growth and results in more activated CD8(+) T cells intratumorally. Together, these data suggest that TGF-beta within the tumor microenvironment induces a population of TAN with a protumor phenotype. TGF-beta blockade results in the recruitment and activation of TANs with an antitumor phenotype.

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PMID:
19732719
[PubMed - indexed for MEDLINE]
PMCID:
PMC2754404
Free PMC Article

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