Tumor-Associated Monocytes/Macrophages Impair NK-Cell Function via TGFβ1 in Human Gastric Cancer
Tumor-Associated Monocytes/Macrophages Impair NK-Cell Function via TGFβ1 in Human Gastric Cancer
复制标题
人类胃癌中肿瘤相关单核细胞/巨噬细胞通过 TGF beta 1 损害 NK 细胞功能
DOI：
10.1158/2326-6066.cir-16-0152
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发表时间：
2017-03-01
影响因子：
10.1
通讯作者：
Zhuang, Yuan
中科院分区：
文献类型：
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作者：
Peng, Liu-sheng;Zhang, Jin-yu;Zhuang, Yuan
自然杀伤（NK）细胞是人类癌症中宿主抗肿瘤免疫应答的主要组分。然而，NK细胞在胃癌中的性质、功能调节和临床相关性在很大程度上仍然未知。在这项研究中，我们发现肿瘤中NK细胞的百分比显著降低，肿瘤浸润NK细胞的低百分比与生存率低和疾病进展呈正相关。尽管NK细胞上的激活和抑制受体的表达在肿瘤和非肿瘤组织之间没有差异，但肿瘤中的NK细胞具有受损的效应子功能，其特征在于IFN γ、TNF α和Ki-67表达降低。我们发现肿瘤浸润的单核细胞/巨噬细胞在物理上接近NK细胞，它们的百分比与IFN γ（+）和TNF α（+）NK细胞百分比呈负相关。体外研究表明，分离的肿瘤相关单核细胞/巨噬细胞可损害IFN γ、TNF α和Ki-67的NK细胞表达。阻断TGF β 1可减弱这种单核细胞/巨噬细胞介导的NK细胞功能损害。我们的数据表明，人NK细胞功能受损的肿瘤相关的单核细胞/巨噬细胞，恢复NK细胞功能可能是一个重要的治疗策略，以防止胃癌的肿瘤免疫逃逸。(C)2017年AACR。
Natural killer (NK) cells are a major component of the host antitumor immune response in human cancer. However, the nature, functional regulation, and clinical relevance of NK cells in gastric cancer remain largely unknown. In this study, we showed that the percentages of NK cells in tumors were significantly decreased, and low percentages of tumor-infiltrating NK cells were positively correlated with poor survival and disease progression. Although the expression of activating and inhibitory receptors on NK cells was shown to be not different between tumor and nontumor tissues, NK cells in tumors had impaired effector functions, characterized by decreased IFN gamma, TNF alpha, and Ki-67 expression. We found that tumor-infiltrating monocytes/macrophages were physically close to NK cells, and their percentages negatively correlated with IFN gamma(+) and TNF alpha(+) NK-cell percentages. Ex vivo study showed that isolated tumor-associated monocytes/macrophages could impair NK-cell expression of IFN gamma, TNF alpha, and Ki-67. Blockade of TGF beta 1 attenuated such monocytes/macrophages-mediated impairment of NK-cell function. Our data suggest that human NK-cell function was impaired by tumorassociated monocytes/macrophages, and that restoring NKcell function may be an important therapeutic strategy to prevent tumor immune escape in gastric cancer. (C) 2017 AACR.