Immunochemical and functional analysis of HLA class II antigens induced by recombinant immune interferon on normal epidermal melanocytes.

Abstract

The effect of recombinant immune interferon (IFN-gamma) on the expression and shedding of HLA antigens and of melanoma-associated antigens (MAA) by epidermal melanocytes was investigated by using serologic and immunochemical techniques. IFN-gamma enhances the expression and/or shedding of HLA class I antigens and of the cytoplasmic MAA defined by monoclonal antibody (MoAb) 465.12S and induces a slight reduction in the expression of the high m.w. melanoma-associated antigen (HMW-MAA). In agreement with the data in the literature, melanocytes incubated with IFN-gamma acquire HLA-DR, -DQ, and -DP antigens. Contrary to previous information in the literature, the effect is not restricted to HLA class II antigens, since IFN-gamma also induces the expression of the 96-kDa MAA recognized by MoAb CL203. The effect of IFN-gamma on HLA class II antigens and 96-kDa MAA is dose and time dependent and is specific, because recombinant leukocyte interferon affects the expression of neither type of antigen. In spite of the expression of HLA class II antigens, IFN-gamma-treated melanocytes do not acquire the ability to stimulate the proliferation of allogeneic lymphocytes. HLA-DR antigens are more susceptible to induction by IFN-gamma than HLA-DQ and -DP antigens, since the percentage of melanocytes acquiring HLA-DQ and -DP antigens is lower than that acquiring HLA-DR antigens. Furthermore, the dose of IFN-gamma is higher and the time of incubation is longer to induce HLA-DQ and -DP antigens than to induce HLA-DR antigens. The differential susceptibility of HLA-DR, -DQ, and -DP antigens as well as of melanocytes from various donors to the modulating effect of IFN-gamma may provide an explanation for the more frequent detection of HLA-DR than of HLA-DQ and -DP antigens in melanoma lesions and for the expression of HLA class II antigens by some, but not all, melanoma lesions.

Polycomb repressor complex 2 suppresses interferon-responsive MHC-II expression in melanoma cells and is associated with anti-PD-1 resistance

“…Previous groups have demonstrated that normal epithelial cells [35][36][37] and other cancer-progenitor cell types, like melanocytes, 38 will express MHC-II under inflammatory conditions, suggesting a non-pathogenic function in immune homeostasis. However, the function of these non-professional antigen presenting cells (non-pAPCs) expressing MHC-II has not been clearly defined.…”

Increased Histological Tumor Pigmentation in Uveal Melanoma Is Related to Eye Color and Loss of Chromosome 3/BAP1

“… 37 , 38 , 39 , 40 , 41 Expression of HLA class II molecules has been reported in normal skin melanocytes upon stimulation with interferon γ. 42 , 43 , 44 …”

MLLT6 maintains PD‐L1 expression and mediates tumor immune resistance

“…The loss of IFN‐γ signaling reduces the efficacy of adoptive cell transfer and checkpoint blockade immunotherapy (Patel et al , 2017) but IFN‐γ also promotes the development of regulatory T cells (Tregs) (Agnello et al , 2003) and upregulates the expression of PD‐L1 and IDO1 to convey pro‐tumorigenic effects (Zaidi & Merlino, 2011). Concomitantly, intratumoral IFN‐γ was shown to be associated with expression of MHC class II molecules (Alspach et al , 2019), which in turn correlates with a more aggressive phenotype in human melanomas (Tsujisaki et al , 1987; Brocker et al , 1988; Hemon et al , 2011). Thus, a compelling interest in identifying modulators of IFN‐γ signaling in tumors has emerged.…”