Identification of Novel Low-Density Neutrophil Markers Through Unbiased High-Dimensional Flow Cytometry Screening in Non-Small Cell Lung Cancer Patients.
Identification of Novel Low-Density Neutrophil Markers Through Unbiased High-Dimensional Flow Cytometry Screening in Non-Small Cell Lung Cancer Patients.
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通过无sall肺细胞肺癌患者的无偏高维流式细胞仪筛查来鉴定新型低密度中性粒细胞标记。
DOI：
10.3389/fimmu.2021.703846
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发表时间：
2021
影响因子：
7.3
通讯作者：
Kargl J
中科院分区：
文献类型：
--
作者：
Valadez-Cosmes P;Maitz K;Kindler O;Raftopoulou S;Kienzl M;Santiso A;Mihalic ZN;Brcic L;Lindenmann J;Fediuk M;Pichler M;Schicho R;Houghton AM;Heinemann A;Kargl J
中性粒细胞被描述为具有促肿瘤和抗肿瘤特性的表型异质细胞类型。最近，从外周血单核细胞（PBMC）部分分离的嗜中性粒细胞的子集已被描述在癌症患者。这些低密度中性粒细胞（LDN）显示出异质性成熟状态，并与成熟的高密度中性粒细胞（HDN）相比具有促肿瘤特性。然而，需要进行额外的研究来表征该细胞群。在这里，我们展示了新的表面标志物，使我们能够区分非小细胞肺癌（NSCLC）患者的LDN和HDN，并评估其作为诊断/预后工具的潜力。LDN在NSCLC患者中高度富集（中位数= 20.4%，范围0.3-76.1%; n=26），但在健康个体中不富集（中位数= 0.3%，范围0.1-3.9%; n=14）。使用一个高维度的人类细胞表面标记筛选，我们确定了12个表面标记，在LDN下调相比HDN，而41个表面标记在LDN子集上调。使用流式细胞术，我们证实了CD 36，CD 41，CD 61和CD 226在LDN组分中的过表达。总之，我们的数据支持LDN是一种独特的中性粒细胞群体的概念，并提供了新的靶点来阐明其在肿瘤进展中的作用及其作为诊断和治疗工具的潜力。
Neutrophils have been described as a phenotypically heterogeneous cell type that possess both pro- and anti-tumor properties. Recently, a subset of neutrophils isolated from the peripheral blood mononuclear cell (PBMC) fraction has been described in cancer patients. These low-density neutrophils (LDNs) show a heterogeneous maturation state and have been associated with pro-tumor properties in comparison to mature, high-density neutrophils (HDNs). However, additional studies are necessary to characterize this cell population. Here we show new surface markers that allow us to discriminate between LDNs and HDNs in non-small cell lung cancer (NSCLC) patients and assess their potential as diagnostic/prognostic tool. LDNs were highly enriched in NSCLC patients (median=20.4%, range 0.3-76.1%; n=26) but not in healthy individuals (median=0.3%, range 0.1-3.9%; n=14). Using a high-dimensional human cell surface marker screen, we identified 12 surface markers that were downregulated in LDNs when compared to HDNs, while 41 surface markers were upregulated in the LDN subset. Using flow cytometry, we confirmed overexpression of CD36, CD41, CD61 and CD226 in the LDN fraction. In summary, our data support the notion that LDNs are a unique neutrophil population and provide novel targets to clarify their role in tumor progression and their potential as diagnostic and therapeutic tool.
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影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
--
作者：
HACBARTH, E;KAJDACSYBALLA, A
通讯作者：
KAJDACSYBALLA, A
影响因子：
5.7
作者：
Bade, Brett C.;Dela Cruz, Charles S.
通讯作者：
Dela Cruz, Charles S.
影响因子：
16.6
作者：
Bronte V;Brandau S;Chen SH;Colombo MP;Frey AB;Greten TF;Mandruzzato S;Murray PJ;Ochoa A;Ostrand-Rosenberg S;Rodriguez PC;Sica A;Umansky V;Vonderheide RH;Gabrilovich DI
通讯作者：
Gabrilovich DI
影响因子：
20.3
作者：
Gekas, Christos;Graf, Thomas
通讯作者：
Graf, Thomas