A different representation of natural T cells and natural killer cells between tumor-infiltrating and periphery lymphocytes in human hepatocellular carcinoma
A different representation of natural T cells and natural killer cells between tumor-infiltrating and periphery lymphocytes in human hepatocellular carcinoma
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DOI：
10.3892/ol.2017.5808
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发表时间：
2017-05-01
期刊：
影响因子：
2.9
通讯作者：
Xu, Wengui
中科院分区：
文献类型：
--
作者：
Li, Xia-Feng;Dai, Dong;Xu, Wengui
自然T细胞[分化簇(CD)3(+)CD56(+)]和自然杀伤(NK)细胞(CD3(-)CD56(+))在人体肝脏中特别丰富，在肝脏的免疫反应中起重要作用。本研究的目的是广泛地确定人肝细胞癌(HCC)中自然T和NK细胞的表型和功能特征。采用多色荧光激活细胞分选技术，从肝癌患者的肿瘤和非肿瘤组织浸润性淋巴细胞(TILs和NILs)和外周血单个核细胞(PBMC)中检测天然墨汁细胞的频率和表型。自然T细胞6.315+/-1.002，NK细胞6.324+/-1.559，自然T细胞6.324+/-1.559，NK细胞14.52+/-2.336。然而，在肝癌患者与健康捐赠者的PBMC中没有观察到这样的结果。值得注意的是，TIL中相当一部分自然T细胞(21.96+/-5.283)获得了叉头盒P3(FOXP3)的表达，FOXP3自然T细胞失去了干扰素-γ和穿孔素的表达。相反，与传统的FOXP3(+)调节性T细胞类似，FOXP3(+)自然T细胞呈现CD25(+)、CD45RO(+)和细胞毒性T淋巴细胞相关蛋白4(+)的特殊表型。与表型转换一致，目前的功能结果表明，FOXP3在自然T细胞中的表达有助于获得强大的免疫抑制能力。综上所述，本研究描述了自然T细胞和NK细胞在局部肿瘤组织和肝癌患者外周血中的不同表达，并发现了一种自发产生于肝癌TIL中的新型FOXP3表达的自然T细胞。
Natural T cells [cluster of differentiation (CD) 3(+)CD56(+)] and natural killer (NK) cells (CD3(-)CD56(+)) are particularly abundant in the human liver and serve an important role in immune responses in the liver. The aim of the present study was to extensively determine the phenotypic and functional characteristics of natural T and NK cells in human hepatocellular carcinoma (HCC). Tumorous and non-tumorous tissue infiltrating lymphocytes (TILs and NILs, respectively) and peripheral blood mononuclear cells (PBMCs) from patients with hepatocellular carcinoma (HCC) were obtained to determine the frequency and phenotype of natural INK cells by a multicolor fluorescence activated cell sorting analysis. The abundance of natural T cells and NK cells was decreased in TILs vs. NILs (natural T cells, 6.315 +/- 1.002 vs. 17.16 +/- 1.804; NK cells, 6.324 +/- 1.559 vs. 14.52 +/- 2.336, respectively). However such results were not observed in PBMCs from HCC patients vs. that of healthy donors. Notably, a substantial fraction of the natural T cells (21.96 +/- 5.283) in TILs acquired forkhead box P3 (FOXP3) expression, and the FOXP3 natural T cells lost the expression of interferon-gamma and perforin. Conversely, being similar to the conventional FOXP3(+) regulatory T cells, the FOXP3(+) natural T cells assumed a specific phenotype that was characteristic of CD25(+), CD45RO(+) and cytotoxic T-Iymphocyte-associated protein 4(+). Consistent with the phenotypic conversion, the present functional results indicate that FOXP3 expression in natural T cells contributes to the acquisition of a potent immunosuppressive capability. In conclusion, the present study describes a different representation of natural T cells and NK cells in local tumor tissues and in the periphery blood of patients with HCC, and identified a new type of FOXP3-expressing natural T cell spontaneously arising in the TILs of HCC.