Immunological escape mechanisms in pancreatic carcinoma.
Malignancies have developed several strategies to evade immune surveillance. We have investigated pancreatic cancer cell lines and pancreatic cancer surgical specimens to evaluate possibilities of tumor escape in the Fas system, and local immune suppression. Despite Fas expression the majority of cell lines was resistant to Fas-mediated apoptosis. The Fas-associated phosphatase-1 is a strong candidate to confer Fas resistance in pancreatic cancer cells. In addition, all investigated pancreatic cancer cell lines and cancer specimens expressed Fas ligand. Fas ligand was functional in cancer cell lines as shown by coculture assays of pancreatic cancer cell lines with Jurkat cells as targets. Additional local immune suppression was demonstrated by loss of T-cell receptor/CD3-zeta chain of pancreatic cancer infiltrating T-lymphocytes. We conclude that these tumor escape mechanisms may contribute to the poor prognosis of pancreatic cancer but also represent targets for new treatment modalities.
Research Unit for Molecular Oncology, Clinic for General Surgery and Thoracic Surgery, Christian Albrechts University, Kiel, Germany.
H
H
Ungefroren
M
M
Voss
W V
WV
Bernstorff
A
A
Schmid
B
B
Kremer
H
H
Kalthoff
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D017209:Apoptosis; D002352:Carrier Proteins; D053222:Fas Ligand Protein; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology; D054645:Protein Phosphatase 1; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D013602:T-Lymphocytes, Cytotoxic; D014407:Tumor Cells, Cultured; D019014:fas Receptor
D002352:Carrier Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D019014:fas Receptor; D054645:Protein Phosphatase 1; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases