Human urinary bladder transitional cell carcinomas acquire the functional Fas ligand during tumor progression.
The interaction between FasL on tumor cells and Fas on lymphocytes may represent a tumor immune escape mechanism. We explored FasL expression and function in human urinary bladder transitional cell carcinomas (TCCs). FasL expression was observed in situ in 45% of TCCs (n = 45) and was absent in normal urothelium (n = 20). A correlation existed between FasL expression and high tumor grade (0% in G1, 14% in G2, and 75% in G3; P < 0.0001) and stage (13% in superficial Ta-T1 versus 81% in invasive T2-T4; P < 0.0001). FasL function was shown by the ability of two FasL-positive primary culture TCC cell lines (established from two FasL-positive invasive TCCs) to induce Fas-mediated killing not only of conventional Fas-sensitive targets (such as Jurkat cells or phytohemagglutinin-lymphoblasts), but also of autologous T lymphocytes generated in a mixed lymphocyte tumor-cell culture. In addition, an association between FasL expression by TCC cells and activated caspase-8, -9, and -3 expression by interferon-gamma-producing CD8-positive tumor-infiltrating lymphocytes was observed in situ. Our results show a functional expression of TCC-expressed FasL that correlates with tumor progression. These results suggest that TCC-expressed FasL may induce apoptosis of anti-tumor T lymphocytes in vivo, providing new insights on the mechanisms involved in bladder TCC progression.
Chopin
Dominique
D
Service d'Urologie et Groupe d'Etude des Tumeurs Urologiques Equipe Mixte INSERM 03-37, Centre Hôspitalier Universitaire Henri Mondor, Créteil, France.
Barei-Moniri
Reza
R
Maillé
Pascale
P
Le Frère-Belda
Marie-Aude
MA
Muscatelli-Groux
Béatrice
B
Merendino
Nicolò
N
Lecerf
Laure
L
Stoppacciaro
Antonella
A
Velotti
Francesca
F
D015703:Antigens, CD / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D053222:Fas Ligand Protein; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics*; D009367:Neoplasm Staging; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D019459:Urothelium / Q000166:cytology / Q000473:pathology
D015703:Antigens, CD; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins