TY - JOUR
T1 - Foxp3 expression in pancreatic carcinoma cells as a novel mechanism of immune evasion in cancer
AU - Hinz, Sebastian
AU - Pagerols-Raluy, Laia
AU - Oberg, Hans Heinrich
AU - Ammerpohl, Ole
AU - Grüssel, Sandra
AU - Sipos, Bence
AU - Grützmann, Robert
AU - Pilarsky, Christian
AU - Ungefroren, Hendrik
AU - Saeger, Hans Detlev
AU - Klöppel, Günter
AU - Kabelitz, Dieter
AU - Kalthoff, Holger
PY - 2007/9/1
Y1 - 2007/9/1
N2 - The forkhead transcription factor Foxp3 is highly expressed in CD4+CD25+ regulatory T cells (Treg) and was recently identified as a key player in mediating their inhibitory functions. Here, we describe for the first time the expression and function of Foxp3 in pancreatic ductal adenocarcinoma cells and tumors. Foxp3 expression was induced by transforming growth factor-β2 (TGF-β2), but not TGF-β1 stimulation in these cells, and was partially suppressed following antibody-mediated neutralization of TGF-β2. The TGF-β2 effect could be mimicked by ectopic expression of a constitutively active TGF-β type I receptor/ALK5 mutant. Down-regulation of Foxp3 with small interfering RNA (siRNA) in pancreatic carcinoma cells resulted in the up-regulation of interleukin 6 (IL-6) and IL-8 expression, providing evidence for a negative transcriptional activity of Foxp3 also in these epithelial cells. Coculture of Foxp3-expressing tumor cells with naive T cells completely inhibited T-cell proliferation, but not activation, and this antiproliferative effect was partially abrogated following specific inhibition of Foxp3 expression. These findings indicate that pancreatic carcinoma cells share growth-suppressive effects with Treg and suggest that mimicking Treg function may represent a new mechanism of immune evasion in pancreatic cancer.
AB - The forkhead transcription factor Foxp3 is highly expressed in CD4+CD25+ regulatory T cells (Treg) and was recently identified as a key player in mediating their inhibitory functions. Here, we describe for the first time the expression and function of Foxp3 in pancreatic ductal adenocarcinoma cells and tumors. Foxp3 expression was induced by transforming growth factor-β2 (TGF-β2), but not TGF-β1 stimulation in these cells, and was partially suppressed following antibody-mediated neutralization of TGF-β2. The TGF-β2 effect could be mimicked by ectopic expression of a constitutively active TGF-β type I receptor/ALK5 mutant. Down-regulation of Foxp3 with small interfering RNA (siRNA) in pancreatic carcinoma cells resulted in the up-regulation of interleukin 6 (IL-6) and IL-8 expression, providing evidence for a negative transcriptional activity of Foxp3 also in these epithelial cells. Coculture of Foxp3-expressing tumor cells with naive T cells completely inhibited T-cell proliferation, but not activation, and this antiproliferative effect was partially abrogated following specific inhibition of Foxp3 expression. These findings indicate that pancreatic carcinoma cells share growth-suppressive effects with Treg and suggest that mimicking Treg function may represent a new mechanism of immune evasion in pancreatic cancer.
UR - http://www.scopus.com/inward/record.url?scp=34548590227&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-06-3304
DO - 10.1158/0008-5472.CAN-06-3304
M3 - Article
C2 - 17804750
AN - SCOPUS:34548590227
SN - 0008-5472
VL - 67
SP - 8344
EP - 8350
JO - Cancer Research
JF - Cancer Research
IS - 17
ER -
