HLA-G EXPRESSION IN MELANOMA - A WAY FOR TUMOR-CELLS TO ESCAPE FROM IMMUNOSURVEILLANCE

Considering the well established role of non-classical HLA-G class I m olecules in inhibiting natural killer (NK) cell function, the conseque nce of abnormal HLA-G expression in malignant cells should be the esca pe of tumors from immunosurveillance. To examine this hypothesis, we a nalyzed HLA-G expression and NK sensitivity in human malignant melanom a cells. Our analysis of three melanoma cell lines and ex vivo biopsy demonstrated that (i) IGR and M74 human melanoma cell lines exhibit a high level of HLA-G transcription with differential HLA-G isoform tran scription and protein expression patterns, (ii) a higher level of HLA- G transcription ex vivo is detected in a skin melanoma metastasis biop sy compared with a healthy skin fragment from the same individual, and (iii) HLA-G protein isoforms other than membrane-bound HLA-G1 protect IGR from NK lysis. It thus appears of critical importance to consider the specific role of HLA-G expression in tumors in the design of futu re cancer immunotherapies.