Clinical significance of decreased zeta chain expression in peripheral blood lymphocytes of patients with head and neck cancer

Patients with squamous cell carcinoma of the head and neck (SCCHN) frequent ly have impaired immune responses. Alterations in T-cell receptor-associate d signaling molecules in tumor-infiltrating as well as circulating lymphocy tes have been reported in these patients. Using quantitative flow cytometry analysis, we have demonstrated that expression of the zeta chain is signif icantly decreased relative to normal controls in both CD8(+) and CD4(+) T c ells as well as CD3(-)CD56(+)CD16(+) natural killer cells in the peripheral blood of patients with SCCHN who, as a result of previous therapies, have no evident disease. Patients with a more aggressive type of SCCHN and those who experienced a recurrence or had a second primary cancer within the las t 2 years of the study had the lowest zeta chain expression. In addition, S CCHN patients showed a significantly greater spontaneous ex vivo apoptosis, as measured by a terminal deoxynucleotide transferase-mediated dUTP nick e nd labeling assay, in PBMCs, compared to normal controls. The observed decr eased expression of zeta in T and natural killer cells coincided but did no t directly correlate with significantly increased spontaneous apoptosis of lymphocytes obtained from treated patients with no evident disease, The res ults suggest that in patients with SCCHN, zeta chain defects and lymphocyte apoptosis are manifestations of long-lasting negative effects of tumor on the immune system.