Tumor-specific up-regulation of the nonclassical class IHLA-G antigen expression in renal carcinoma

HLA-G is a nonclassical class I antigen mainly expressed at the maternofeta l interface during pregnancy where it is thought to downmodulate maternal i mmune response against the semiallogeneic fetus. Recent studies indicate th at ectopic up-regulation of HLA-G expression on melanoma cells may also fav or their escape from antitumor immune response. HLA-G expression was here i nvestigated on paraffin-embedded tumor and adjacent normal renal tissues of 18 renal cell carcinoma (RCC) patients. We provide evidence that HLA-G ant igen is differentially expressed in carcinoma and normal renal cells and th at up-regulation of this antigen in the tumor cells is more frequent than a lterations of other MHC class I or class II antigens. We also demonstrated that HLA-G cell surface expression and secretion is maintained in a tumor c ell line (DM) established from an HLA-G-positive RCC lesion. Furthermore, w e show that type I (alpha and beta) and, in particular, type II (gamma) IFN treatment enhances steady-state mRNA levels and cell surface expression of HLA-G in the DM cell line. As several studies suggest that HLA-G displays various functional features that allow down-modulation of immune response i n vitro, we propose that selective in vivo expression of HLA-G may particip ate in the impairment of antitumor immunity in RCC.