Impaired ζ chain expression and IFN-γ production in peripheral blood T and NK cells of patients with advanced lung cancer

Abstract

Recent studies show that low expression of zeta chain in T and NK cell leads to impaired anti-tumour immunity in patients with cancer, poor prognosis, and shorter overall survival. Therefore, monitoring zeta chain expression may be useful in assessing immune competence in lung cancer patients and in following changes during anticancer therapies. Such studies concerning small-cell and non-small cell lung cancer (SCLC and NSCLC, respectively) have not been published so far. The expression of zeta chain and IFN-gamma in peripheral blood (PB) T and NK cells from SCLC and NSCLC patients at advanced (III, IV) stages were analysed before and after chemotherapy with etoposide and cisplatin using flow cytometry. Serum concentrations of TGF-beta1 and IL-10 were also estimated at each time point tested. Before therapy, impaired zeta chain expression was observed in all the patients corresponding with increased levels of immuno-suppressive cytokines in sera compared with controls. Decreased IFN-gamma production in T cells from all patients was also demonstrated. In NK cells, IFN-gamma was secreted at lower levels in NSCLC patients, while in the SCLC group it was normal. After chemotherapy, restoration of zeta expression in NK cells and its insignificant increase in T cells in SCLC patents corresponding with normalization of TGF-beta secretion were noted. In contrast, NSCLC patients retained impaired zeta expression in T and NK cells. SCLC and NSCLC patients showed a profound defect in IFN-gamma secretion in T and NK cells upon treatment. There were no differences in studied parameters between NSCLC and SCLC groups before and after chemotherapy. This is the first report of impaired zeta expression in PB T and NK cells in patients with SCLC and NSCLC in advanced stages, which may result from higher levels of immunosuppressive cytokines in sera. After cytostatic treatment, all the studied patients, including those with initial good response to chemotherapy, remained with profound abnormalities in T and NK cells, which could have dramatic consequences regarding severely impaired anti-tumour immunity.