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

doi:10.1016/j.ccr.2009.06.017

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 journal › Article › peer-review

2464 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 language	English
Pages (from-to)	183-194
Number of pages	12
Journal	Cancer Cell
Volume	16
Issue number	3
DOIs	https://doi.org/10.1016/j.ccr.2009.06.017
State	Published - 8 Sep 2009
Externally published	Yes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.ccr.2009.06.017

Cite this

@article{eb249f3d42e44c98acac071c9aaa1449,

title = "Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: {"}N1{"} versus {"}N2{"} TAN",

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.",

keywords = "CELLCYCLE, MOLIMMUNO",

author = "Fridlender, {Zvi G.} and Jing Sun and Samuel Kim and Veena Kapoor and Guanjun Cheng and Leona Ling and Worthen, {G. Scott} and Albelda, {Steven M.}",

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. ",

year = "2009",

month = sep,

day = "8",

doi = "10.1016/j.ccr.2009.06.017",

language = "אנגלית",

volume = "16",

pages = "183--194",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β

T2 - "N1" versus "N2" TAN

AU - Fridlender, Zvi G.

AU - Sun, Jing

AU - Kim, Samuel

AU - Kapoor, Veena

AU - Cheng, Guanjun

AU - Ling, Leona

AU - Worthen, G. Scott

AU - Albelda, Steven M.

N1 - 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.

PY - 2009/9/8

Y1 - 2009/9/8

N2 - 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.

AB - 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.

KW - CELLCYCLE

KW - MOLIMMUNO

UR - http://www.scopus.com/inward/record.url?scp=69249222379&partnerID=8YFLogxK

U2 - 10.1016/j.ccr.2009.06.017

DO - 10.1016/j.ccr.2009.06.017

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 19732719

AN - SCOPUS:69249222379

SN - 1535-6108

VL - 16

SP - 183

EP - 194

JO - Cancer Cell

JF - Cancer Cell

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this