Liu Yangyang, Hu Yue, Gu Feifei, Liang Jinyan, Zeng Yulan, Hong Xiaohua, Zhang Kai, Liu Li
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Oncotarget. 2017 Jun 28;8(53):90969-90978. doi: 10.18632/oncotarget.18771. eCollection 2017 Oct 31.
An immunosuppressive subgroup of neutrophils, low density neutrophils (LDNs) was reported to be closely related to several diseases. This study was designed to explore the association between LDNs and advanced lung adenocarcinoma, as well as potential mechanisms.
The expression levels of surface CD molecules on LDNs were different from high density neutrophils (HDNs), consistent with previous studies. The ratio of LDNs/HDNs, rather than the percentage of LDNs in peripheral blood mononuclear cells (PBMCs), was significantly higher in lung adenocarcinoma patients than healthy controls. It was also observed that the ratio decreased when patients received anti-cancer treatments, and increased when disease relapsed. Patients harboring positive epidermal growth factor receptor (EGFR) mutation had significantly higher ratios. Both the ratio and the percentage showed positive correlation with CD8+ T cells. Although significantly increased TGF-β was detected in lung adenocarcinoma patients, relationship between TGF-β and LDNs was not obvious.
LDNs and HDNs levels of peripheral blood from 52 lung adenocarcinoma patients and 13 healthy controls were determined by flow cytometry. Lymphocytes and cytokines were also detected.
Two kinds of neutrophils with different phenotypes were identified in lung adenocarcinoma patients. Besides, we found the existence of high ratio of LDNs/HDNs in these patients, which is related to disease prognosis, EGFR mutation and bad immune status.
据报道,中性粒细胞的一个免疫抑制亚群,即低密度中性粒细胞(LDNs)与多种疾病密切相关。本研究旨在探讨LDNs与晚期肺腺癌之间的关联及其潜在机制。
LDNs表面CD分子的表达水平与高密度中性粒细胞(HDNs)不同,这与先前的研究一致。肺腺癌患者中LDNs/HDNs的比值显著高于健康对照组,而非外周血单个核细胞(PBMCs)中LDNs的百分比。还观察到,患者接受抗癌治疗时该比值下降,疾病复发时则升高。表皮生长因子受体(EGFR)突变阳性的患者比值显著更高。该比值和百分比均与CD8+T细胞呈正相关。虽然在肺腺癌患者中检测到TGF-β显著升高,但TGF-β与LDNs之间的关系并不明显。
采用流式细胞术测定52例肺腺癌患者和13例健康对照者外周血中LDNs和HDNs的水平。同时检测淋巴细胞和细胞因子。
在肺腺癌患者中鉴定出两种具有不同表型的中性粒细胞。此外,我们发现这些患者中存在较高的LDNs/HDNs比值,这与疾病预后、EGFR突变及不良免疫状态有关。