PMID- 16288283
OWN - NLM
STAT- MEDLINE
DCOM- 20060523
LR  - 20220318
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 11
IP  - 12
DP  - 2005 Dec
TI  - Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent 
      antitumor immunity.
PG  - 1314-21
AB  - The immune system can act as an extrinsic suppressor of tumors. Therefore, tumor 
      progression depends in part on mechanisms that downmodulate intrinsic immune 
      surveillance. Identifying these inhibitory pathways may provide promising targets 
      to enhance antitumor immunity. Here, we show that Stat3 is constitutively 
      activated in diverse tumor-infiltrating immune cells, and ablating Stat3 in 
      hematopoietic cells triggers an intrinsic immune-surveillance system that 
      inhibits tumor growth and metastasis. We observed a markedly enhanced function of 
      dendritic cells, T cells, natural killer (NK) cells and neutrophils in 
      tumor-bearing mice with Stat3(-/-) hematopoietic cells, and showed that tumor 
      regression requires immune cells. Targeting Stat3 with a small-molecule drug 
      induces T cell- and NK cell-dependent growth inhibition of established tumors 
      otherwise resistant to direct killing by the inhibitor. Our findings show that 
      Stat3 signaling restrains natural tumor immune surveillance and that inhibiting 
      hematopoietic Stat3 in tumor-bearing hosts elicits multicomponent therapeutic 
      antitumor immunity.
FAU - Kortylewski, Marcin
AU  - Kortylewski M
AD  - H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, 
      Florida 33612, USA.
FAU - Kujawski, Maciej
AU  - Kujawski M
FAU - Wang, Tianhong
AU  - Wang T
FAU - Wei, Sheng
AU  - Wei S
FAU - Zhang, Shumin
AU  - Zhang S
FAU - Pilon-Thomas, Shari
AU  - Pilon-Thomas S
FAU - Niu, Guilian
AU  - Niu G
FAU - Kay, Heidi
AU  - Kay H
FAU - Mule, James
AU  - Mule J
FAU - Kerr, William G
AU  - Kerr WG
FAU - Jove, Richard
AU  - Jove R
FAU - Pardoll, Drew
AU  - Pardoll D
FAU - Yu, Hua
AU  - Yu H
LA  - eng
GR  - P01 CA082533/CA/NCI NIH HHS/United States
GR  - R01 CA089693/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20051120
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Bone Marrow Cells/*immunology
MH  - Cell Line, Tumor
MH  - Cytotoxicity Tests, Immunologic
MH  - Dendritic Cells/*immunology
MH  - Flow Cytometry
MH  - Gene Silencing
MH  - Immunohistochemistry
MH  - Killer Cells, Natural/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Neoplasms/*immunology
MH  - STAT3 Transcription Factor/*genetics/metabolism
MH  - Signal Transduction/genetics/*immunology
MH  - T-Lymphocyte Subsets/*immunology
MH  - T-Lymphocytes/*immunology
EDAT- 2005/11/17 09:00
MHDA- 2006/05/24 09:00
CRDT- 2005/11/17 09:00
PHST- 2005/06/28 00:00 [received]
PHST- 2005/10/13 00:00 [accepted]
PHST- 2005/11/17 09:00 [pubmed]
PHST- 2006/05/24 09:00 [medline]
PHST- 2005/11/17 09:00 [entrez]
AID - nm1325 [pii]
AID - 10.1038/nm1325 [doi]
PST - ppublish
SO  - Nat Med. 2005 Dec;11(12):1314-21. doi: 10.1038/nm1325. Epub 2005 Nov 20.