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干扰素 α-2b 部分纠正了舌鳞癌患者单核细胞/巨噬细胞中失调的 CC 受体/配体。

Dysregulated CC receptor/ligand in monocytes/macrophages from tongue squamous cell carcinoma patients is partially rectified by interferon α-2b.

机构信息

Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, Kolkata 700026, India.

出版信息

Hum Immunol. 2012 Jan;73(1):38-47. doi: 10.1016/j.humimm.2011.10.015. Epub 2011 Oct 29.

Abstract

In an aim to rectify dysregulated CC chemokine receptor (CCR5)/ligand (RANTES, MIP-1α, MIP-1β) status of monocytes/macrophages in tongue squamous cell carcinoma (TSCC; n = 12) patients, we have tested interferon α2b (IFNα2b), a novel immunomodulator with wide use in the management of several forms of cancer. IFNα2b can upregulate reduced CCR5 expression and increases the suppressed secretory status of its ligands, as evidenced from in vitro studies on monocytes/macrophages from the peripheral blood of TSCC patients as well as healthy individuals. Isolated monocytes of TSCC patients (n = 5) undergoing chemotherapeutic treatment along with IFNα2b immunotherapy demonstrated significant upregulation in CCR5 expression and secretion of corresponding ligands. These rectifications in receptor/ligand levels are reflected in improved CCR5-dependent migration of monocytes/macrophages after IFNα2b treatment. The rectified chemokine profile and cellular migration translate into better tumoricidal and antigen-presenting functions of these cells. Accordingly, enhanced T-cell-mediated tumor cell killing is demonstrated upon IFNα2b treatment. Translating dual benefits on monocyte/macrophage functions, IFNα2b may emerge as a potential form of immunotherapy for TSCC patients that may be combined with standard chemotherapy for better clinical outcome.

摘要

为了纠正舌鳞状细胞癌 (TSCC; n = 12) 患者单核细胞/巨噬细胞中失调的 CC 趋化因子受体 (CCR5)/配体 (RANTES、MIP-1α、MIP-1β) 状态,我们测试了干扰素 α2b (IFNα2b),这是一种新型免疫调节剂,广泛用于多种癌症的治疗。IFNα2b 可以上调降低的 CCR5 表达,并增加其配体的抑制分泌状态,这在来自 TSCC 患者和健康个体外周血的单核细胞/巨噬细胞的体外研究中得到了证实。接受化疗和 IFNα2b 免疫治疗的 TSCC 患者 (n = 5) 的分离单核细胞显示 CCR5 表达和相应配体的分泌显著上调。受体/配体水平的这些校正反映在 IFNα2b 治疗后单核细胞/巨噬细胞的 CCR5 依赖性迁移得到改善。修正的趋化因子谱和细胞迁移转化为这些细胞更好的杀肿瘤和抗原呈递功能。因此,在 IFNα2b 治疗后,T 细胞介导的肿瘤细胞杀伤作用增强。IFNα2b 对单核细胞/巨噬细胞功能具有双重益处,可能成为 TSCC 患者潜在的免疫治疗形式,可与标准化疗联合使用以获得更好的临床结果。

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