Allogeneic lymphocyte responses to B7-1 expressing human cancer cell lines.
Recent studies suggest that expression of B7-1 by tumor cells is effective at inducing antitumor immune responses. Our purpose was to transfect three human cancer cell lines (MEWO, WM35, and H125) with a B7-1 expression plasmid and test the immunogenicity of these modified cancer cells using allogeneic human peripheral blood lymphocytes (PBLs). PBLs were tested in vitro for both proliferative and cytotoxic activity against parental and B7-transfected tumor cells. [3H]thymidine lymphocyte proliferation assays showed that PBLs incubated with B7-1+ WM35 [major histocompatibility complex (MHC) class I+II+ melanoma] demonstrated a substantial increase in T cell proliferation (P < 0.0005), but PBLs incubated with B7-1+ MEWO (MHC class I-II- melanoma) and H125 (MHC class I+II- lung adenosquamous carcinoma) did not. T-cell-mediated cytotoxicity was not increased against B7-1+ tumor cells: effector T lymphocytes primed against B7-1+ tumor cells did not show any increase in cytolytic activity against 51Cr-labeled B7-1+ or B7-1- target cells. NK cells did not lyse MEWO cells, but they did kill H125 and WM35 targets. B7-1 expression on MEWO and WM35 cells did not result in enhanced lysis by NK cells, but NK cytotoxicity was enhanced by B7-1 expression on H125 cells (P < 0.01). The observation that NK cytotoxicity is enhanced by B7-1+ H125 cells suggests that B7-1/CD28 interactions may be important in NK cytotoxic activity. We conclude that B7-1+ WM35 cells, which express both MHC molecules and antigenic epitopes, elicit an improved alloantigen-induced T cell proliferative response, presumably because they have the capacity to deliver an adequate antigen-specific signal which can be costimulated by B7-1/CD28 interaction.
Dessureault
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Department of Surgery, Mount Sinai Hospital, Samuel Lunenfeld Research Institute, University of Toronto, Ontario, Canada.
Gallinger
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D000917:Antibody Formation; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D000939:Epitopes; D018014:Gene Transfer Techniques; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D000939:Epitopes; D015395:Histocompatibility Antigens Class I