HLA-G expression in human melanoma cells: protection from NK cytolysis

Expression of the non-classical HLA-G class I antigen is physiologically re stricted to a limited number of tissues including trophoblasts, and is thou ght to play a role in establishing tolerance of the fetus by the maternal i mmune system. We investigated whether ectopic expression of HLA-G could als o be detected in tumor cells and confer them the ability to escape immune c ytotoxic responses. High levels of all alternatively spliced HLA-G transcri pts could be detected in melanoma cells by RT-PCR. Analysis of biopsies fro m a melanoma patient revealed a higher HLA-G transcription level in skin me tastasis as compared to healthy skin, while specific amplification of the H LA-GS transcript was only observable in the tumor. HLA-G protein expression could also be detected in two melanoma cell lines. HLA-G-positive tumors i nhibit cytotoxic lysis by the NK cell line YT2C2-PR. This inhibition is not observed with B-EBV cell lines bearing matched class I specificities, and is thought to occur through interaction of HLA-G with inhibitory receptors that are distinct from known KIRs interacting with HLA-E or classical class I molecules. Together, these results confirm that HLA-G expression at the surface of tumor cells can participate in the evasion of antitumoral immune responses and favor tumor progression. (C) 1999 Elsevier Science Ireland L td. All rights reserved.