title: IFNalpha2b stimulated release of IFNgamma differentially regulates T cell and NK cell mediated tumor cell cytotoxicity.
abstract: Interferonalpha2b (IFNalpha2b) augments the suppressed immune functions and peripheral blood mononuclear cell (PBMC) cytotoxicity of head and neck squamous cell carcinoma (HNSCC) patients by differential regulation of IFNgamma, a pleotropic Th1 cytokine. In the present communication, we have examined the role of IFNgamma in IFNalpha2b initiated T and NK cell mediated cytotoxicity of tumor cells. IFNalpha2b activates both T and NK cells to release IFNgamma. IFNgamma plays a crucial role in enhancing tumor cell cytotoxicity by T cells, but not by NK cells, as evidenced by killing of a oral (KB) and breast (MCF7) cancer cells, without affecting the killing of NK sensitive erythroleukemic K562 cells by IFNalpha2b activated PBMC. IFNalpha2b driven tumor cell cytotoxicity is related to the rectification of the downregulated expression of cytotoxic molecules, perforin, granzyme B and FasL in CD8+ T and CD56+ NK cells. Expression of IFNalpha2b mediated perforin and granzyme B is dependent on IFNgamma in T cells, but not in NK cells. However, expression of FasL in both T and NK cells is not dependent on IFNgamma. In conclusion, IFNalpha2b enhances suppressed T cell cytotoxicity of HNSCC patients by stimulating perforin-granzyme B system, which is IFNgamma dependent. IFNalpha2b also induces the expression of perforin-granzyme B system in NK cells, but this NK mediated cytotoxicity is IFNgamma independent.
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, 37, S.P. Mookherjee Road, Kolkata 700026, India.
authors.forename: Anamika
authors.initials: A
authors.lastname: Bose
authors.forename: Rathindranath
authors.initials: R
authors.lastname: Baral
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D053804:Granzymes / Q000096:biosynthesis; D006258:Head and Neck Neoplasms / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000097:blood / Q000494:pharmacology*; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D053222:Fas Ligand Protein; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011994:Recombinant Proteins; D054353:Perforin; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma; D053804:Granzymes