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

Interferonα2b (IFNα2b) 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 IFNγ, a pleotropic Th1 cytokine. In the present communication, we have examined the role of IFNγ in IFNα2b initiated T and NK cell mediated cytotoxicity of tumor cells. IFNα2b activates both T and NK cells to release IFNγ. IFNγ 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 IFNα2b activated PBMC. IFNα2b 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 IFNα2b mediated perforin and granzyme B is dependent on IFNγ in T cells, but not in NK cells. However, expression of FasL in both T and NK cells is not dependent on IFNγ. In conclusion, IFNα2b enhances suppressed T cell cytotoxicity of HNSCC patients by stimulating perforin–granzyme B system, which is IFNγ dependent. IFNα2b also induces the expression of perforin–granzyme B system in NK cells, but this NK mediated cytotoxicity is IFNγ independent.