Pancreatic cancer cells can evade immune surveillance via nonfunctional Fas (APO-1/CD95) receptors and aberrant expression of functional Fas ligand

Wolfram V. Bernstorff, Remco A. Spanjaard, Allen K. Chan, Diane C. Lockhart, Noriaki Sadanaga, Isabelle Wood, Matthias Peiper, Peter S. Goedegebuure, Timothy J. Eberlein

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

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.

Original languageEnglish
Pages (from-to)73-84
Number of pages12
JournalSurgery
Volume125
Issue number1
DOIs
StatePublished - 1999

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