IRX-2, a novel immunotherapeutic, enhances and protects NK-cell functions in cancer patients |
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Authors: | B Schilling E S Halstead P Schuler M Harasymczuk J E Egan T L Whiteside |
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Institution: | Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA. |
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Abstract: | Background IRX-2 is a primary biologic which has been used for the therapy of head and neck squamous cell cancer (HNSCC) with promising clinical results. Since NK-cell function is compromised in HNSCC patients, we tested the effects of IRX-2 on the restoration of human NK-cell functions in vitro. Methods Peripheral blood mononuclear cells (PBMC) were isolated from 23 HNSCC patients and 10 normal controls (NC). The NK-cell phenotype and functions were compared before and after culture?±?IRX-2 or?±?50?IU/ml rhIL-2. Flow cytometry was used to study the NK-cell phenotype, cytotoxic activity and cytokine expression. Results Impaired NK-cell cytotoxicity in HNSCC patients was related to lower expression of NKG2D, NKp30 and NKp46 receptors (P?0.05) and not to a decreased frequency of NK cells. Incubation of patients’ NK cells with IRX-2 up-regulated the percentage of receptor-positive NK cells (P?0.05). It also up-regulated cytotoxicity of patients’ NK cells (P?0.01) more effectively than rhIL-2 (P?0.01). IRX-2, but not rhIL-2, protected NK cells from suppression mediated by TGF-β, and it restored (P?0.05) expression of activating NK-cell receptors and NK-cell cytotoxicity suppressed by TGF-β. Expression of pSMAD was decreased in NK cells treated with IRX-2 but not in those treated with rhIL-2. Conclusions IRX-2 was more effective than IL-2 in enhancing NK-cell cytotoxicity and protecting NK-cell function of HNSCC patients in vitro, emphasizing the potential advantage of IRX-2 as a component of future therapies for HNSCC. |
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