Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: "N1" versus "N2" TAN

Zvi G. Fridlender*, Jing Sun, Samuel Kim, Veena Kapoor, Guanjun Cheng, Leona Ling, G. Scott Worthen, Steven M. Albelda

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2383 Scopus citations

Abstract

TGF-β blockade significantly slows tumor growth through many mechanisms, including activation of CD8+ T cells and macrophages. Here, we show that TGF-β 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-β 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-β within the tumor microenvironment induces a population of TAN with a protumor phenotype. TGF-β blockade results in the recruitment and activation of TANs with an antitumor phenotype.

Original languageAmerican English
Pages (from-to)183-194
Number of pages12
JournalCancer Cell
Volume16
Issue number3
DOIs
StatePublished - 8 Sep 2009
Externally publishedYes

Bibliographical note

Funding Information:
This work was funded by NCI PO1 CA 66726, NHLBI T32 HL07586, NHLBI RO1 HL068876, and NIEHS P30 ES013508-02. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS or NIH.

Keywords

  • CELLCYCLE
  • MOLIMMUNO

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