Reduction in susceptibility to natural killer cell-mediated lysis of human FO-1 melanoma cells after induction of HLA class I antigen expression by transfection with B2m gene.

Abstract

Induction of HLA class I antigens on cultured melanoma cells FO-1 after transfection with a human or a mouse B2m gene was associated with a statistically significant reduction in their susceptibility to natural killer (NK) cell-mediated lysis. These results indicate that the structural differences between human and mouse 62-M do not abolish the ability of the HLA class I molecular complex to modulate NK cell-mediated lysis ofmelanoma cells FO-1. The role of HLA class I antigens in the phenomenon is corroborated by the ability of anti-HLA class I MAb to enhance, although to a different extent, the susceptibility of transfected FO-1 cells to NK cell-mediated lysis. Gamma interferon (IFN-'y) and tumor necrosis factor-a (TNF-a) significantly reduced the susceptibility to NK cell-mediated lysis of transfected FO-1 cells. Surprisingly, TNF-a reduced the extent of lysis more than IFN-'y, although the latter cytokine enhanced HLA class I antigen expression more than the former one. This finding, in conjunction with a reduction in the susceptibility to NK cell-mediated lysis of untransfected FO-1 cells incubated with IFN-'y or TNF-a, suggests that the two cytokines reduce NK cell-mediated lysis of transfected cells by modulating not only the expression of HLA class I antigens, but also that of other structures. Induction of HLA class I antigens and their modulation with IFN-'y did not affect the susceptibility to lymphokine-activated killer (LAK) cell-mediated lysis of transfected FO-1 cells. Characterization of the molecular mechanism(s) underlying abnormalities in HLA class I antigen expression by melanoma cells and of the role of these molecules in the interactions of melanoma cells with various types of effector cells may suggest novel immunotherapeutic approaches to melanoma. (J. Clin. Invest. 1991. 88:282-289.)

Interferon-γ-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression

“…19,20 IFNg is known to modulate expression of immunomodulary molecules on tumor cells [21][22][23] and we therefore examined whether stimulation of tumor cells with IFNg- affected expression of ligands known to be involved in NK cell recognition. As shown in Supplementary Figure 4, we measured the effect of activated NK supernatant or IFNg on the expression of MHC Class I, b2M, HLA-C, HLA-A2, NKG2D, NKP44, NKP46, NKP30 ligands, MICA/B, DNAM-1 ligands (CD112, CD155), 2B4 ligand (CD48), TRAIL ligands (TRAIL-R1, TRAIL-R2) and Fas ligand (CD95) in six tumor cell lines and primary MM, AML and ALL cells.…”

IFN-Dependent Down-Regulation of the NKG2D Ligand H60 on Tumors

“…The importance of IFN-␥ in enhancing tumor immunogenicity in vivo has been shown, at least in part, to be due to increased MHC class I pathway activity in the tumor targets leading to their more effective recognition by CD8 ϩ T cells. It is also known that IFN-␥ decreases tumor cell recognition by NK cells in vitro (5)(6)(7)(8)(9)(10)(11)(12). Thus, even though NK cells are known to play critical roles in regulating growth of primary and transplantable tumors (13,14), the precise mechanisms controlling their participation in IFN-␥-dependent tumor rejection remain undefined.…”

Cancer testis antigens expression in mesothelioma: role of DNA methylation and bioimmunotherapeutic implications

“…The anti-NY-ESO-1 rabbit antiserum was obtained from 20-week-old NZW female rabbit immunised at weekly intervals with subcutaneous injections of 1 mg of recombinant NY-ESO-1 protein. Immunoprecipitation, SDS -PAGE, and Western blotting were performed as described (Maio et al, 1991).…”