New insights revealed a critical role for endogenously produced IFNɣ in promoting host responses to tumors. In this sense, molecular mechanisms underlying immune dysfunction that include the role of IFNɣ in immune responses are not clearly defined in breast cancer.
PBL of breast cancer patients and healthy controls were analyzed for IFNɣ 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 IFNɣ 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 IFNɣ level in PBL and NK cell activity was found, while there was no correlation between the IFNɣ 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, IFNα showed this effect also in patients and controls.
In this study we show that, in breast cancer patients, lower IFNɣ level and reduced NK cell cytotoxicity, important in the control of tumor growth, are associated with tumor progression. These results indicate that IFNɣ level and NK cell cytotoxicity may represent possible targets in designing new therapeutic agents in this disease.
Clinical trial identification
Legal entity responsible for the study
National Projects funded by Ministry of Science Government of Serbia
Ministry of Science
All authors have declared no conflicts of interest.