Preferential expansion of pro-inflammatory Tregs in human non-small cell lung cancer.
Preferential expansion of pro-inflammatory Tregs in human non-small cell lung cancer.
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DOI：
10.1007/s00262-015-1725-1
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Khazaie K
中科院分区：
文献类型：
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作者：
Phillips JD;Knab LM;Blatner NR;Haghi L;DeCamp MM;Meyerson SL;Heiferman MJ;Heiferman JR;Gounari F;Bentrem DJ;Khazaie K
肺癌是美国癌症相关死亡的主要原因。调节性T细胞（Tregs）通常起调节免疫反应和减少炎症的作用。先前的研究已经证明不同的treg亚群具有不同的抗炎或促炎特性。本研究旨在确定Treg亚群在非小细胞肺癌（NSCLC）患者中的分布和特征。在手术切除前采集健康对照（HC）和非小细胞肺癌患者的外周血，分离单个核细胞，用流式细胞术染色和分析。treg通过CD4和CD25的表达来定义，分为CD45RA+Foxp3int （naïve, Fr. I）或CD45RA−Foxp3hi（激活Fr. II）。活化的常规T细胞为CD4+CD45RA−Foxp3int （Fr. III）。从23例HC和26例NSCLC患者中采集样本。从非小细胞肺癌患者中分离的Tregs被发现对初始T细胞具有增强的抑制功能。癌症患者激活Tregs的频率显著增加（分数II: FrII），分别为17.5%和3.2% （P < 0.001）。与HC的Tregs相比，FrII Tregs的rorγ - t和IL17表达增加，IL10表达减少，显示出促炎特征。这项研究表明，一种具有促炎特征的Tregs新亚群在非小细胞肺癌患者中优先扩增。这个Treg亚群似乎与先前报道的人类结肠癌患者和息肉病小鼠模型中的促炎性Treg相同。我们预计肺癌中的促炎Treg参与疾病的免疫发病机制，并提出靶向该Treg亚群可能对非小细胞肺癌具有保护作用。
Lung cancer is the leading cause of cancer-related death in the USA. Regulatory T cells (Tregs) normally function to temper immune responses and decrease inflammation. Previous research has demonstrated different subsets of Tregs with contrasting anti- or pro-inflammatory properties. This study aimed to determine Treg subset distributions and characteristics present in non-small cell lung cancer (NSCLC) patients. Peripheral blood was collected from healthy controls (HC) and NSCLC patients preceding surgical resection, and mononuclear cells were isolated, stained, and analyzed by flow cytometry. Tregs were defined by expression of CD4 and CD25 and classified into CD45RA+Foxp3int (naïve, Fr. I) or CD45RA−Foxp3hi (activated Fr. II). Activated conventional T cells were CD4+CD45RA−Foxp3int (Fr. III). Samples from 23 HC and 26 NSCLC patients were collected. Tregs isolated from patients with NSCLC were found to have enhanced suppressive function on naive T cells. Cancer patients had significantly increased frequencies of activated Tregs (fraction II: FrII), 17.5 versus 3.2 % (P < 0.001). FrII Tregs demonstrated increased RORγt and IL17 expression and decreased IL10 expression compared to Tregs from HC, indicating pro-inflammatory characteristics. This study demonstrates that a novel subset of Tregs with pro-inflammatory characteristics preferentially expand in NSCLC patients. This Treg subset appears identical to previously reported pro-inflammatory Tregs in human colon cancer patients and in mouse models of polyposis. We expect the pro-inflammatory Tregs in lung cancer to contribute to the immune pathogenesis of disease and propose that targeting this Treg subset may have protective benefits in NSCLC.