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- W4361948913 abstract "<div>Abstract<p><b>Purpose:</b> To assess the extent of signal transducer and activator of transcription (STAT) activation in response to interleukin 2 (IL-2) in melanoma patients' T cells, along with clinical stage of tumor progression.</p><p><b>Experimental Design:</b> T lymphocytes from peripheral blood of healthy donors and of American Joint Committee on Cancer stage I to IV melanoma patients, as well as from metastatic lymph nodes of patients, were evaluated for responsiveness to IL-2. CFSE assays and single-cell phospho-STAT–specific flow cytometry screening were used.</p><p><b>Results</b>. T cells from advanced melanoma patients, in comparison with healthy donors, showed reduced proliferation to IL-2 and IL-15, but not to anti-CD3 monoclonal antibody. Impaired response occurred in CCR7<sup>+</sup> and CCR7<sup>−</sup> T-cell subsets, but not in CD3<sup>−</sup> CD8<sup>+</sup> natural killer (NK) cells, and was not explained by induction of apoptosis, increased cytokine consumption, or altered IL-2R subunit expression in patients' T lymphocytes. By phospho-specific flow cytometry, defective STAT1 and STAT5 activation in response to IL-2 was found mainly in T lymphocytes from peripheral blood and/or tumor site of American Joint Committee on Cancer stage III and IV patients, compared with stage I and II patients and to donors, and in melanoma antigen-specific T cells isolated from metastatic lymph nodes. At tumor site, impaired STAT activation in T cells did not correlate with frequency of CD4<sup>+</sup> CD25<sup>+</sup> Foxp3<sup>+</sup> T cells. Serum from advanced melanoma patients inhibited IL-2–dependent STAT activation in donors' T cells and a neutralizing monoclonal antibody to transforming growth factor β1 counteracted such inhibition.</p><p><b>Conclusions:</b> These results provide evidence for development of impaired STAT signaling in response to IL-2, along with clinical evolution of the disease, in melanoma patients' T cells.</p></div>" @default.
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- W4361948913 date "2023-03-31" @default.
- W4361948913 modified "2023-10-14" @default.
- W4361948913 title "Data from Impaired STAT Phosphorylation in T Cells from Melanoma Patients in Response to IL-2: Association with Clinical Stage" @default.
- W4361948913 doi "https://doi.org/10.1158/1078-0432.c.6517348.v1" @default.
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