期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 29, 期 2, 页码 635-641出版社
ELSEVIER
DOI: 10.1016/j.intimp.2015.09.017
关键词
T cell immunoglobulin- and mucin-domain-containing molecule-3; Natural killer cells; Cytotoxicity; Human lung adenocarcinoma
资金
- Important Science & Technology Specific Projects of Zhejiang Province [2012C13015-3, 2012C13015-1]
- Zhejiang Provincial Natural Science Foundation of China [LQ13H100001]
- Cultivation of High-level Innovative Health Talents Program of Zhejiang Province
T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) has been shown to play an important role in mediating NK-cell function in human diseases. However, the relationship between Tim-3 expression in natural killer (NK) cells and human lung adenocarcinoma remains unclear. We therefore investigated the expression of Tim-3 in NK cells and explored the effect of Tim-3 blockade on NK cell-mediated activity in human lung adenocarcinoma. Upregulated expression of Tim-3 on CD3-CD56 + cells (P < 0.05) and CD3-CD56(dim) cells (P < 0.05) of patients with lung adenocarcinoma was detected by flow cytometry. Moreover, Tim-3 expression in CD3-CD56+ NK cells was higher in patients with lung adenocarcinoma with lymph node metastasis (LNM) (P < 0.05) or with tumor stage T3-T4 (P < 0.05). Tim-3 expression in CD56(dim) NK-cell subset was higher in patients with tumor size >= 3 cm (P < 0.05), or LNM (P < 0.05) or with tumor stage T3-T4 (P < 0.05). Further analysis showed that higher expressions of Tim-3 on both CD3-CD56 + NK cells and CD56(dim) NK-cell subset were independently correlated with shorter overall survival of patients with lung adenocarcinoma (log-rank test, P = 0.0418, 0.0406, respectively). Importantly, blockade of Tim-3 signaling with anti-Tim-3 antibodies resulted in the increased cytotoxicity and IFN-gamma production of peripheral NK cells from patients with lung adenocarcinoma. Our data indicate that Tim-3 expression in NK cells can function as a prognostic biomarker in human lung adenocarcinoma and support that Tim-3 could be a new target for an immunotherapeutic strategy. (C) 2015 Elsevier B.V. All rights reserved.
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