A B7-1-transfected human melanoma line stimulates proliferation and cytotoxicity of autologous and allogeneic lymphocytes.
B7 co-stimulation is necessary to activate resting T cells upon antigen recognition by the T cell receptor. To see whether expression of B7 may render human melanoma cells able to stimulate T cells, a cloned melanoma line (Me1B6), which did not express B7-1, was transfected with the human B7-1 gene. In proliferation assays, B7-1 transfected cells (Me1B6/B7) showed greater stimulatory activity of allogeneic and autologous peripheral blood lymphocytes (PBL) compared to parental, non-transfected tumor cells. This effect was also seen when allogeneic CD8+ and CD4+ subpopulations were used as effectors. In these studies, activation of lymphocytes was B7-1-dependent and HLA classes I and II mediated. The higher proliferation correlated with an increased lytic activity by PBL stimulated with B7-1+ tumor cells against the untransfected Me1B6. Furthermore, PBL from a metastatic melanoma patient stimulated by Me1B6/B7 developed an higher lytic activity not only against Me1B6 but also against their autologous, B7-1- tumor. Finally, after Me1B6/B7 stimulation, PBL released interleukin (IL)-2 and interferon-gamma, but not IL-4, suggesting a Th1-mediated response. These data support the use of B7-1 transfected melanoma cells in the therapeutic vaccination of melanoma patients.
Sulé-Suso
J
J
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Arienti
F
F
Melani
C
C
Colombo
M P
MP
Parmiani
G
G
D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D009362:Neoplasm Metastasis; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014611:Vaccination
D018122:B7-1 Antigen; D006680:HLA Antigens; D007376:Interleukin-2; D007371:Interferon-gamma