Immune stimulatory potential of B7.1 and B7.2 retrovirally transduced melanoma cells: suppression by interleukin 10.
The immunostimulatory capacities of B7.1-and B7.2- expressing melanoma cells were investigated. A365, 960306 and 950504 melanomas, established from nodular melanoma lesions, were retrovirally transduced. Irradiated B7-, B7.1+ and B7.2+ melanoma cells were co-cultured with autologous or allogeneic peripheral blood mononuclear cells (PBMCs). Proliferation was assessed by [3H]thymidine uptake. mRNA encoding for interleukin 2 (IL-2), IL-4, IL-10 and interferon gamma (IFN-gamma) was determined. IFN-gamma, IL-2, IL-4 and IL-10 secretion were quantitated by ELISA. B7.1+ and B7.2+ melanomas induced proliferation of PBMCs and mRNA for IL-2 and IFN-gamma. After co-incubation of transduced melanoma cells with PBMCs, high levels of IL-10 were detectable in the supernatant. The presence of neutralizing anti-IL-10 antibodies resulted in enhanced proliferation and IL-2 and IFN-gamma secretion. Our data indicate that B7.1- and B7.2-transduced melanoma cells trigger lymphocytic proliferation with transcription of IL-10, IL-2 and IFN-gamma. Blocking of IL-10 augments these effects. Gene therapy protocols using tumour cells as a vaccine have to consider the adverse effects of IL-10.
Dummer
R
R
Department of Dermatology, University of Zurich Medical School, Switzerland.
Yue
F Y
FY
Pavlovic
J
J
Geertsen
R
R
Döhring
C
C
Moelling
K
K
Burg
G
G
D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051940:B7-2 Antigen; D002455:Cell Division; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma