Induction of immunogenicity of a human renal-cell carcinoma cell line by TAP1-gene transfer

Reduced expression of the major-histocompatibility-complex(MHC)-class-I ant igens has been demonstrated in renal-cell carcinoma (RCC), and appeared to be associated with deficiencies in the expression and function of different components of the MHC-class-I-antigen-processing pathway and poor recognit ion by cytotoxic T-lymphocytes (CTL). In order to investigate the role of p eptide transporters for the immunogenic phenotype of RCC, tumor cells were stably transfected with the human TAP1A gene, While the TAP1 transfectants showed heterogeneous TAP1-transgene expression pattern of mRNA and protein, high TAP1 expression and a TAP-controlled increase in MHC-class-I surface expression could be achieved in selected transfectants. IFN-lambda upregula tes the expression of MHC-class-I antigens and TAP1 both in control and in TAP1-transfected RCC cells to a similar level. No additive effect of TAP1 o ver-expression was observed in TAP1 transfectants. Although no enhanced CTL -mediated lysis was obtained, cytokine release was substantially increased in response to TAP1-transfected RCC cells, but not to control cells. Furthe rmore, TAP1 transfectants were able to stimulate the proliferation of allog eneic T cells. These studies suggest that abnormalities of MHC-class-I surf ace expression due to dysfunctional peptide transporters contribute to the immune escape phenotype of RCC cells and that the immune tolerance of RCC c ould be altered by TAP1-gene transfer. (C) 1999 Wiley-Liss, Inc.