IFNα2b stimulated release of IFNγ differentially regulates T cell and NK cell mediated tumor cell cytotoxicity

Interferon alpha 2b (IFN alpha 2b) 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 IFN gamma, a pleotropic Th1 cytokine. In the present communication, we have examined the role of IFN gamma in IFN alpha 2b initiated T and NK cell mediated cytotoxicity of tumor cells. IFN alpha 2b activates both T and NK cells to release IFN gamma. IFN gamma 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 IFN alpha 2b activated PBMC. IFN alpha 2b 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 IFN alpha 2b mediated perforin and granzyme B is dependent on IFN gamma in T cells, but not in NK cells. However, expression of FasL in both T and NK cells is not dependent on IFN gamma. In conclusion, IFN alpha 2b enhances suppressed T cell cytotoxicity of HNSCC patients by stimulating perforin-granzyme B system, which is IFN gamma dependent. IFN alpha 2b also induces the expression of perforin-granzyme B system in NK cells, but this NK mediated cytotoxicity is IFN gamma independent. (c) 2006 Elsevier B.V. All rights reserved.