MHC-dependent cytolysis of autologous tumor cells by lymphocytes infiltrating urothelial carcinomas.
Tumor-infiltrating lymphocytes (TIL) were grown from 23 urothelial carcinomas. Phenotyping analysis showed that the TIL cultures were mainly CD3+. Although CD4+ and CD8+ T-cell sub-sets were grown in culture, CD4+ T-cell sub-sets predominated over CD8+ T cells. Immunohistochemical studies performed on 5 tumor specimens confirmed this observation, and indicated that CD4+ T cells surrounded the tumor islets, whereas CD8+ T lymphocytes were localized among the tumor cells. Five short-term carcinoma cell lines established from these urothelial tumors were used as target cells in cytolysis assays in order to investigate the functional anti-tumor activity of autologous TIL. TIL from 4/5 tumors were lytic and 3 TIL lines displayed MHC-class-I-dependent cytotoxicity directed against autologous tumor cells. CD4+ T-cell-depletion experiments performed on TIL line 07 confirmed that CD8+ MHC-class-I-dependent CTL were the predominant effectors. Finally, experiments performed on 6 allogeneic urothelial-cancer cell lines matched for HLA-class-I molecules showed that TIL07 exhibited selective lytic activity toward tumor 07. These data indicate that CD8+ MHC-class-I-dependent CTL present in urothelial carcinomas are functional and may participate in the anti-tumor immune response.
Housseau
F
F
Laboratory of Tumor Immunology, URA 1484 CNRS, University of Rene Descartes, Paris, France.
Zeliszewski
D
D
Roy
M
M
Paradis
V
V
Richon
S
S
Ricour
A
A
Bougaran
J
J
Prapotnich
D
D
Vallancien
G
G
Benoit
G
G
Desportes
L
L
Bedossa
P
P
Hercend
T
T
Bidart
J M
JM
Bellet
D
D
D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002295:Carcinoma, Transitional Cell / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000473:pathology; D014571:Urologic Neoplasms / Q000276:immunology* / Q000473:pathology
D017252:CD3 Complex; D006680:HLA Antigens