PMID- 19732719
OWN - NLM
STAT- MEDLINE
DCOM- 20091014
LR  - 20231120
IS  - 1878-3686 (Electronic)
IS  - 1535-6108 (Print)
IS  - 1535-6108 (Linking)
VI  - 16
IP  - 3
DP  - 2009 Sep 8
TI  - Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus 
      "N2" TAN.
PG  - 183-94
LID - 10.1016/j.ccr.2009.06.017 [doi]
AB  - 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.
FAU - Fridlender, Zvi G
AU  - Fridlender ZG
AD  - Thoracic Oncology Research Laboratory, 1016B ARC, University of Pennsylvania, 
      Philadelphia, PA 19104-6160, USA. fridlender@hadassah.org.il
FAU - Sun, Jing
AU  - Sun J
FAU - Kim, Samuel
AU  - Kim S
FAU - Kapoor, Veena
AU  - Kapoor V
FAU - Cheng, Guanjun
AU  - Cheng G
FAU - Ling, Leona
AU  - Ling L
FAU - Worthen, G Scott
AU  - Worthen GS
FAU - Albelda, Steven M
AU  - Albelda SM
LA  - eng
GR  - R01 HL105834/HL/NHLBI NIH HHS/United States
GR  - T32 HL007586-24/HL/NHLBI NIH HHS/United States
GR  - P30 ES013508/ES/NIEHS NIH HHS/United States
GR  - R01 HL068876/HL/NHLBI NIH HHS/United States
GR  - R01 HL068876-07/HL/NHLBI NIH HHS/United States
GR  - P30 ES013508-02/ES/NIEHS NIH HHS/United States
GR  - P01 CA066726/CA/NCI NIH HHS/United States
GR  - P01 CA066726-11/CA/NCI NIH HHS/United States
GR  - T32 HL007586/HL/NHLBI NIH HHS/United States
GR  - P01 CA 66726/CA/NCI NIH HHS/United States
GR  - T32 HL07586/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cancer Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 (Antigens, Ly)
RN  - 0 (Azabicyclo Compounds)
RN  - 0 (CD11b Antigen)
RN  - 0 (Cytokines)
RN  - 0 (Ly6G antigen, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (SM16 compound)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
CIN - Cancer Cell. 2009 Sep 8;16(3):173-4. PMID: 19732714
MH  - Animals
MH  - Antigens, Ly/metabolism
MH  - Azabicyclo Compounds/pharmacology
MH  - CD11b Antigen/metabolism
MH  - CD8-Positive T-Lymphocytes/immunology/pathology
MH  - Cell Line, Transformed
MH  - Cell Line, Tumor
MH  - Cell Polarity/genetics/*immunology
MH  - Cell Transformation, Viral
MH  - Cytokines/genetics/immunology
MH  - Immunohistochemistry
MH  - Lung Neoplasms/genetics/immunology/pathology
MH  - Mesothelioma/genetics/immunology/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Neutrophils/*immunology/pathology
MH  - Phenotype
MH  - RNA, Messenger/metabolism
MH  - Receptors, Transforming Growth Factor beta/antagonists & inhibitors
MH  - Transforming Growth Factor beta/genetics/*immunology
MH  - Xenograft Model Antitumor Assays/methods
PMC - PMC2754404
MID - NIHMS130047
EDAT- 2009/09/08 06:00
MHDA- 2009/10/15 06:00
PMCR- 2010/09/08
CRDT- 2009/09/08 06:00
PHST- 2009/01/13 00:00 [received]
PHST- 2009/04/02 00:00 [revised]
PHST- 2009/06/24 00:00 [accepted]
PHST- 2009/09/08 06:00 [entrez]
PHST- 2009/09/08 06:00 [pubmed]
PHST- 2009/10/15 06:00 [medline]
PHST- 2010/09/08 00:00 [pmc-release]
AID - S1535-6108(09)00215-3 [pii]
AID - 10.1016/j.ccr.2009.06.017 [doi]
PST - ppublish
SO  - Cancer Cell. 2009 Sep 8;16(3):183-94. doi: 10.1016/j.ccr.2009.06.017.