CD80-mediated induction of immunostimulation in two ocular melanoma cell lines is augmented by interferon-gamma.
Although the transfection of the T-cell costimulatory molecule CD80 cDNA into human tumours can augment their immunogenicity in vitro, its expression alone is ineffective in many tumour systems. We evaluated the influence of CD80 expression on the immunostimulatory activity of ocular melanoma cell lines and determined whether IFN-gamma could enhance the effect. Two ocular melanoma cell lines were transfected with CD80 cDNA. The immunostimulatory capacity of the CD80+ transfectants was determined by their ability to stimulate the proliferation of allogeneic peripheral blood mononuclear cells (PBMC). The influence of additional accessory molecules on PBMC proliferation was assessed by pre-treating the CD80 transfectants with IFN-gamma. The CD80+ transfectants induced proliferation of allogeneic PBMC. IFN-gamma treatment of the tumour cells induced upregulated expression of MHC class I, de novo expression of MHC class II and CD54, and enhanced the ability of the CD80+ transfectants to stimulate PBMC proliferation. CD4+ T cells were not required for the proliferative response against untreated CD80+ tumour cells but were necessary for the augmentation of proliferation observed following IFN-gamma treatment. CD80+ ocular melanoma cells possess immunostimulatory potential which is augmented by IFN-gamma induced upregulation of cell surface molecules. Further studies on the role of costimulatory molecules in inducing anti-tumour immunity in ocular melanoma may help to define new strategies for application of immunotherapeutic approaches to treat this aggressive disease.
Mulcahy
K A
KA
Section of Oncology and Pathology (Cancer Studies), University of Sheffield Medical School, Beech Hill Road, Sheffield, S10 2RX, UK.
Alexander
S
S
Platts
K E
KE
Wardle
C
C
Sisley
K
K
Rennie
I G
IG
Murray
A K
AK
D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005134:Eye Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008212:Lymphocyte Depletion; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation
D000970:Antineoplastic Agents; D018122:B7-1 Antigen; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma