Association of IFNγ Production and NK Cytotoxicity in PBL of Breast Cancer Patients

New insights revealed a critical role for endogenously produced IFNγ in promoting host responses to tumors. In this sense, molecular mechanisms underlying immune dysfunction that include the role of IFNγ in immune responses are not clearly defined in breast cancer. PBL of breast cancer patients and healthy controls were analyzed for IFNγ expression and NK cell activity using flow cytometry and 51Cr-release assay, respectively. Patients in early clinical stage of breast cancer had significantly decreased NK cell cytotoxicity compared to controls. However, patients with advanced clinical stage had significantly decreased NK cell cytotoxicity compared to early breast cancer patients and controls. Positive correlation was shown between intracellular level of IFNγ in PBL and NK cell activity in both healthy controls and all investigated patients. However, in patients with advanced disease stages positive correlation between intracellular IFNγ level in PBL and NK cell activity was found, while there was no correlation between the IFNγ level in PBL and NK cell activity in patients in early disease stage. IL-2 increased NK cell cytotoxicity in breast cancer patients and control. Furthermore, IFN&agr; showed this effect also in patients and controls. In this study we show that, in breast cancer patients, lower IFNγ level and reduced NK cell cytotoxicity, important in the control of tumor growth, are associated with tumor progression. These results indicate that IFNγ level and NK cell cytotoxicity may represent possible targets in designing new therapeutic agents in this disease.