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Molecular Oncology, Markers, Clinical Correlates |
Chain Expression in Peripheral Blood Lymphocytes of Patients with Head and Neck Cancer1
University of Pittsburgh Cancer Institute [I. K., T. S., J. T. J., T. L. W.] and Departments of Pathology [T. L. W.] and Otolaryngology [J. T. J., T. L. W.], University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213
Patients with squamous cell carcinoma of the head and neck (SCCHN) frequently have impaired immune responses. Alterations in T-cell receptor-associated signaling molecules in tumor-infiltrating as well as circulating lymphocytes have been reported in these patients. Using quantitative flow cytometry analysis, we have demonstrated that expression of the 
chain is significantly decreased relative to normal controls in both CD8+ and CD4+ T cells 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 last 2 years of the study had the lowest chain expression. In addition, SCCHN patients showed a significantly greater spontaneous ex vivo apoptosis, as measured by a terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay, in PBMCs, compared to normal controls. The observed decreased expression of in T and natural killer cells coincided but did not directly correlate with significantly increased spontaneous apoptosis of lymphocytes obtained from treated patients with no evident disease. The results suggest that in patients with SCCHN, chain defects and lymphocyte apoptosis are manifestations of long-lasting negative effects of tumor on the immune system.
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