Different expression of Fas and Fas ligand in tumor infiltrating and peripheral lymphocytes of patients with renal cell carcinomas.
BACKGROUND
The presence of tumor infiltrating lymphocytes (TIL) in renal cell carcinomas (RCC) is thought to reflect a host-mediated immune response against the tumor and the Fas/Fas ligand--based lytic pathway is a major mechanism of T lymphocyte--mediated cytotoxicity. The aim of the present study was to investigate the expression of Fas and Fas ligand (FasL) in freshly-isolated pure TIL as compared to autologous peripheral blood lymphocytes (PBL), in order to determine their activation status.


METHODS
The mRNA expression of Fas and FasL was compared in freshly-isolated CD3(+)-, CD4(+)- and CD8(+)-TIL and matched autologous CD3(+)-, CD4(+)- and CD8(+)-PBL. The TIL were isolated from mechanically disaggregated tumor material and PBL from peripheral blood by gradient centrifugation and subsequent selection with magnetic beads. In these pure lymphocyte preparations the constitutive expression of Fas and FasL was determined by using a semiquantitative PCR-assisted mRNA amplification assay.


RESULTS
In the CD3(+)-TIL of 20 patients with RCC (group 1), mRNA levels of FasL were significantly higher than in the matched autologous CD3(+)-PBL (p < or = 0.01) whereas Fas expression was not different in both populations. In a second group of 20 patients (group 2), we found a significantly higher expression of FasL in the CD8(+)-TIL compared to the CD8(+)-PBL (p < or = 0.001) and also in the CD4(+)-TIL compared to the CD4(+)-PBL (p < or = 0.001).


CONCLUSIONS
The higher expression of FasL in the TIL compared to autologous PBL reflects an in vivo activation and lytic potency of the lymphocytes in the tumor surrounding.
Elsässer-Beile
Ursula
U
Department of Urology, University of Freiburg, Stefan-Meier Str. 8, D-79106 Freiburg, Germany. elsu@klinikum.uni-freiburg.de
Gierschner
Dorothee
D
Welchner
Tanja
T
Wetterauer
Ulrich
U
D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000276:immunology*; D017252:CD3 Complex / Q000096:biosynthesis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000276:immunology*; D053222:Fas Ligand Protein; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D017252:CD3 Complex; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor