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Molecular Oncology, Markers, Clinical Correlates |
University of Pittsburgh Cancer Institute [T. K. H., G. D., T. T., N. M., W. G., 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
Spontaneous apoptosis was observed in a proportion of peripheralblood mononuclear cells obtained from patients withhead and neck cancer (HNC) but not from normal healthy donors (T. Saito et al., Clin. Cancer Res., 5: 1263–1273, 1999). To further investigate this phenomenon, peripheral blood mononuclear cells were obtained from patients with HNC or normal controls (NCs) and evaluated for expression of apoptosis markers (annexin V binding and caspase-3 activation), T-cell receptor-associated 
chain, and the death receptor Fas (APO-1, CD95) in CD3+ T cells by multicolor flow cytometry. Soluble Fas ligand (sFasL) in the sera of these individuals was quantitated by ELISA. In patients with HNC, 74 ± 15% (mean ± SD) of CD3+ T cells were Fas+ compared with 52 ± 13% in NCs (P < 0.0001). Furthermore, 29 ± 16% of the Fas+ CD3+ T cells bound annexin V in patients and only 14% ± 7% of the Fas+ CD3+ T cells bound annexin V in NCs (P < 0.0001). In patients, Fas+ CD3+ cells preferentially underwent apoptosis and showed a loss of chain expression. Significantly greater proportions of CD8+ T cells than CD4+ T cells were apoptotic (P < 0.0002), which indicates that CD8+ T cells were especially sensitive to apoptosis. Serum levels of sFasL were lower in HNC patients with active disease than in NCs or in patients with no evident disease (P < 0.0183). This suggested utilization of sFasL produced in vivo and activation of the Fas/Fas ligand (FasL) pathway in Fas+ T cells. Proportions of apoptotic T cells were higher in HNC patients than in NCs (P < 0.0001), and a subset of HNC patients with active disease had the highest proportions of circulating Fas+ annexin V+ T lymphocytes. The data indicate that the Fas/FasL pathway is involved in spontaneous apoptosis of circulating Fas+ T lymphocytes in cancer patients. Fas/FasL interactions might lead to excessive turnover of T cells in the circulation and, consequently, to reduced immune competence in patients with HNC.
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