Abstract
Background: The Fas (APO-1/CD95) receptor/Fas ligand (FasR/FasL) system plays a key role in immune
surveillance. We investigated the possibility of a tumor escape mechanism involving
the FasR/FasL system in pancreatic cancer cells. Methods: Fourteen pancreatic cancer cell lines and 3 pancreatic cancer surgical specimens
were studied for their expression of FasR and FasL by flow cytometry, immunoblotting,
and immunohistochemistry. FasR function was tested with an anti-FasR antibody. FasL
function was assessed by coculture assays using pancreatic cancer cells and FasR-sensitive
Jurkat T-cells. Results: FasR was expressed in normal pancreas, in 14 of 14 pancreatic cancer cell lines,
and in 3 of 3 surgical specimens. However, only 1 of 14 cancer cell lines expressed
functional FasR when grown in monolayer, although 3 additional cell lines displayed
functional FasR when cultured in suspension. Normal pancreas did not express FasL,
whereas 14 of 14 cancer cell lines and 3 of 3 surgical specimens expressed FasL. FasL
expressed by pancreatic cancer cells mediated killing of Jurkat T-cells in coculture
assays (P < .005). Conclusions: These data suggest that pancreatic cancer cells have 2 potential mechanisms of evading
Fas-mediated immune surveillance. A nonfunctional FasR renders them resistant to Fas-mediated
apoptosis. The aberrant expression of functional FasL allows them to “counterattack”
activated Fas-sensitive T-cells. Alone or in unison, these tumor escape mechanisms
may contribute to the malignant and often rapid course of pancreatic cancer disease.
(Surgery 1999;125:73-84.)
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Article info
Publication history
Accepted:
July 11,
1998
Footnotes
☆Supported by a grant from Dr Mildred Scheel Stiftung für Krebsforschung D/96/17181 (W.v.B.) and in part by National Institutes of Health grant T32CA09535 and National Institutes of Health R01 grants CA 45854 and CA 606662.
☆☆Reprint requests: Timothy J. Eberlein, MD, Bixby Professor and Chairman, Department of Surgery, Washington University School of Medicine, 660 S Euclid Ave, Box 8109, St Louis, MO 63110.
Identification
Copyright
© 1999 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
