Protective effects of interferon-γ on squamous-cell carcinoma of head and neck targets in antibody-dependent cellular cytotoxicity mediated by human natural killer cells
✍ Scribed by Myung-Whun Sung; Jonas T. Johnson; Guus Van Dongen; Theresa L. Whiteside
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 740 KB
- Volume
- 66
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
An in vitro model of antibody-dependent cellular qtotoxicity (ADCC) was established, using squamous-cell carcinoma of the head and neck (SCCHN) targets, humanlmouse chimeric monoclonal adbodies (cMAbs) SF-25 and 323/A3 and human peripheral blood mononuclear cells (PBMC). We previously showed that natural killer (NK) cells am the main effector population mediating ADCC in the presence of the cMAbs. ADCC was signiflcantly inhibited by the overnight pre-treatment of SCCHN targets with exogenous interferony (1FN-y). This inhibition was doce-dependent, reproducible and consistently observed with various SCCHN cell lines. SCCHN cells pre-treated with I F N y had a significantly higher expression of intercellular adhesion molecule-I (ICAM-I) and major histocompatibility complex (MHC) class I antigem compared with untreated target cells. No dffarences in expression of the SCCHN-associated antigens on these targets or in the formation of NK-SCCHN conjugates were found, using flow cytometry. IFNypre-treated SCCHN cells were less effectii in competing with untreated targets in cold target inhibition assays and in inducing cytokine producdon from NK cells in co-incubation experiments. Proteahre effects of I F N y on target cell sensithrlty to lysis were blocked by pre-treatment of target cells with actinomycin-D or cycloheximidc. The suxeptibili of the target cells was restored by removal of MHC class I antigens from their surface by acid stripping before ADCC. Our results suggest that the decreased ADCC seen with SCCHN targets pre-treated with IFNy is related to post-binding events, possibly altered signaling from targets to effector cells, and requires protein synthesis in the target cells.