Elsevier

Surgery

Volume 125, Issue 1, January 1999, Pages 73-84
Surgery

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

https://doi.org/10.1016/S0039-6060(99)70291-6Get rights and content

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.)

Section snippets

Cell lines and pancreatic cancer tissue collection

MPanc-9621 and BW-1 are human pancreatic cancer cell lines derived from surgical specimens obtained with institutional review board approval. Normal pancreatic and confirmed pancreatic cancer specimens were supplied by Dr R. Odze (Department of Pathology, Brigham and Women's Hospital, Boston, Mass). Pancreatic cancer cell lines AsPc-1, BxPc-3, Capan-1, Capan-2, CFPAC-1, Colo-587, HPAF-2, Hs700T, Hs766T, MiaPaCa-2, Panc-1, Su86.86, mouse embryo fibroblast cell line 3T6 (Swiss albino), the Daudi

FasR is expressed in pancreatic cancer

All 14 pancreatic cancer cell lines expressed FasR as detected by flow cytometry (Fig 1, a , Table I).

. Flow cytometric analyses of FasR, iFasL and mFasL. FasR was analyzed on a 3-decade log scale; all other analyses were done on a 4-decade log scale. Black lines represent control staining; gray-filled curves represent specific staining of (a ) FasR, (b ) iFasL, and (c ) mFasL. Percentage positive cells and MFI (mn) are given for each cell line. *In these cases where the curves show only 1

Discussion

The data shown in this study suggest that pancreatic cancer cells may use 2 mechanisms of evading Fas-mediated immune surveillance. First, pancreatic cancer cells may resist Fas-mediated apoptosis by expressing a nonfunctional FasR. Second, most, if not all, pancreatic cancer cells aberrantly express functional FasL and can induce apoptosis in Fas-sensitive activated T-cells.

Other reports have shown a down-regulation or loss of FasR expression in human breast cancer cell lines,26 hepatoma cell

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    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.

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