Apoptosis of circulating CD8+ T lymphocytes is a frequent finding in patients with cancer. T-cell output by the thymus or antigen-driven expansion of circulating T cells could compensate for apoptosis and thus normalize their homeostasis. We studied the frequency of recent thymic emigrants (RTE) identified by T-cell receptor excision circles (TREC) and of naive and memory T-cell subsets in peripheral blood samples obtained from 39 patients with head and neck cancer (HNC) and 33 age-matched controls (NC). TREC numbers were determined by real-time quantitative PCR, and CD8+CD45RO-CD27+ or CD4+CD45RO-CD27+ T-cell subsets were quantified by flow cytometry. Age-associated decreases in TREC numbers and proportions of naive CD8+ and CD4+ T-cell subsets were significantly greater in cancer patients than NC. In contrast, the memory compartment was expanded, with increased proportions of CD4+CD45RO+ but not CD8+CD45RO+ T cells, in cancer patients vs. NC. These alterations did not normalize in patients who were NED. The data suggest that lower thymic output combined with rapid turnover of naive CD8+ T cells account for altered lymphocyte homeostasis in HNC patients. The defect persists long after curative treatments and may contribute to immune cell dysregulation in patients with cancer.
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http://dx.doi.org/10.1016/j.clim.2004.12.011 | DOI Listing |
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