Pancreatic cancer cells can evade immune surveillance via nonfunctional Fas (APO-1/CD95) receptors and aberrant expression of functional Fas ligand.
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.
von Bernstorff
W
W
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass., USA.
Spanjaard
R A
RA
Chan
A K
AK
Lockhart
D C
DC
Sadanaga
N
N
Wood
I
I
Peiper
M
M
Goedegebuure
P S
PS
Eberlein
T J
TJ
D017209:Apoptosis; D002448:Cell Adhesion; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007157:Immunologic Surveillance; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D010179:Pancreas / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics / Q000502:physiology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor