PMID- 16286245
OWN - NLM
STAT- MEDLINE
DCOM- 20060118
LR  - 20210103
IS  - 1535-6108 (Print)
IS  - 1535-6108 (Linking)
VI  - 8
IP  - 5
DP  - 2005 Nov
TI  - TGF-beta directly targets cytotoxic T cell functions during tumor evasion of 
      immune surveillance.
PG  - 369-80
AB  - Tumors escape from immune surveillance by producing the immunosuppressive 
      cytokine TGF-beta. However, the mechanism by which TGF-beta inhibits T 
      cell-mediated tumor clearance in vivo is unknown. We demonstrate that TGF-beta 
      acts on cytotoxic T lymphocytes (CTLs) to specifically inhibit the expression of 
      five cytolytic gene products-namely, perforin, granzyme A, granzyme B, Fas 
      ligand, and interferon gamma-which are collectively responsible for CTL-mediated 
      tumor cytotoxicity. Repression of granzyme B and interferon-gamma involves 
      binding of TGF-beta-activated Smad and ATF1 transcription factors to their 
      promoter regions, indicating direct and selective regulation by the TGF-beta/Smad 
      pathway. Neutralization of systemic TGF-beta in mice enables tumor clearance with 
      restoration of cytotoxic gene expression in antigen-specific CTLs in vivo. We 
      suggest that TGF-beta suppresses CTL function in vivo through an anticytotoxic 
      program of transcriptional repression.
FAU - Thomas, Dori A
AU  - Thomas DA
AD  - Cancer Biology and Genetics Program and Howard Hughes Medical Institute, Memorial 
      Sloan-Kettering Cancer Center, New York, New York 10021, USA.
FAU - Massague, Joan
AU  - Massague J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 (Activating Transcription Factors)
RN  - 0 (Blood Proteins)
RN  - 0 (Interleukin-2)
RN  - 0 (Smad Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.21.- (Granzymes)
RN  - EC 3.4.21.- (Gzmb protein, mouse)
RN  - EC 3.4.21.- (Serine Endopeptidases)
SB  - IM
CIN - Cancer Cell. 2005 Nov;8(5):349-50. PMID: 16286241
MH  - Activating Transcription Factors/metabolism
MH  - Animals
MH  - Blood Proteins/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cytotoxicity, Immunologic/*genetics
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Granzymes
MH  - Interferon-gamma/metabolism
MH  - Interleukin-2/physiology
MH  - Mice
MH  - Serine Endopeptidases/metabolism
MH  - Smad Proteins/metabolism
MH  - T-Lymphocytes, Cytotoxic/metabolism/*physiology
MH  - Transforming Growth Factor beta/*physiology
MH  - *Tumor Escape
EDAT- 2005/11/16 09:00
MHDA- 2006/01/19 09:00
CRDT- 2005/11/16 09:00
PHST- 2005/04/26 00:00 [received]
PHST- 2005/09/28 00:00 [revised]
PHST- 2005/10/20 00:00 [accepted]
PHST- 2005/11/16 09:00 [pubmed]
PHST- 2006/01/19 09:00 [medline]
PHST- 2005/11/16 09:00 [entrez]
AID - S1535-6108(05)00331-4 [pii]
AID - 10.1016/j.ccr.2005.10.012 [doi]
PST - ppublish
SO  - Cancer Cell. 2005 Nov;8(5):369-80. doi: 10.1016/j.ccr.2005.10.012.