CD80-mediated induction of immunostimulation in two ocular melanoma cell lines is augmented by interferon-γ

Abstract

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.

A Synergistic Antitumor Effect of Interleukin-2 Addition with CD80 Immunogene Therapy for Peritoneal Metastasis of Gastric Carcinoma

“…Several reports have indicated that CD80 geneinfected tumor cells can stimulate PBMC activity as effector cells [29,30]. CD80 delivers an important costimulatory signal via binding to its receptor, CD28 and CTLA-4 [29,31,32]. Cancer cells can escape from preexisting CTLs either by a loss of tumor antigen or by down-regulation of costimulatory molecules.…”