Dendritic cells (DC) are potent antigen-presenting cells that initiate and regulate T-cell responses. In this study, the numbers and functional cytokine secretions of plasmacytoid and myeloid DC (pDC and mDC, respectively) in peripheral blood from young and elderly subjects were compared. Overall, pDC numbers in peripheral blood were lower in healthy elderly compared with healthy young subjects (p = 0.016). In response to influenza virus stimulation, isolated pDC from healthy elderly subjects secreted less interferon (IFN)–α compared with those from healthy young subjects. The decline in IFN-α secretion was associated with a reduced proportion of pDC that expressed Toll-like receptor–7 or Toll-like receptor-9. In contrast, there was little difference in the numbers and cytokine secretion function between healthy young and healthy elderly subjects (p = 0.82). However, in peripheral blood from frail elderly subjects, the numbers of mDC were severely depleted as compared with either healthy young or elderly subjects (p = 0.014 and 0.007, respectively). Thus, aging was associated with the numerical and functional decline in pDC, but not mDC, in healthy young versus elderly subject group comparisons, while declining health in the elderly can profoundly impact mDC negatively. Because of the importance of pDC for antiviral responses, the age-related changes in pDC likely contribute to the impaired immune response to viral infections in elderly persons, especially when combined with the mDC dysfunction occurring in those with compromised health.

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BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL), nasal-type, is a distinct entity of lymphoid tissue. ENKTL is sensitive to radiotherapy (RT), but the prognosis is poorer than for other types of early lymphoma. The treatment schedule is controversial. METHODS: A phase 2 study was conducted of ''sandwich'' protocols, with earlier RT after an initial 2 to 3 cycles of LVP (L-asparaginase, vincristine, and prednisone), followed by further ''consolidation'' cycles. Patients aged 18 years and older who had previously untreated ENKTL and localized lesions in the upper aerodigestive tract were enrolled. The primary endpoints were objective response rate and complete remission rate. The secondary endpoints were 2-year overall survival, 2-year progression-free survival, and toxicity. This study is registered with www.Chictr.org, number ChicTR-TNC-00000394, and is ongoing for long-term follow-up. RESULTS: Twenty-six patients completed total therapy, which resulted in 88.5% response that included 21 patients (80.8%) with complete response (CR) and 2 patients (7.7%) with partial response. Three (11.5%) of 26 patients progressed during therapy. With a median follow-up of 27 months (range, 4-35 months), the 2-year overall survival was 88.5%, and the 2-year progression-free survival was 80.6%. Patients with CR had better prognosis than patients without CR. Only 2 patients (7.7%) experienced grade 3 leukocytopenia. No grade 4 toxicity or treatment-related deaths were observed. CONCLUSIONS: The research showed that the ''sandwich'' protocol of LVP combined with RT was a safe and effective treatment for localized nasal natural killer/T-cell lymphoma, and the results warrant further investigation into this protocol. Cancer 2012;118:3294-

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