PDF(Pubmed)
Abstract：
Due to their abundance in the blood, low RNA content, and short lifespan, neutrophils have been classically considered to be one homogenous pool. However, recent work has found that mature neutrophils and neutrophil progenitors are composed of unique subsets exhibiting context-dependent functions. In this study, we ask if neutrophil heterogeneity is associated with melanoma incidence and/or disease stage.
Using mass cytometry, we profiled melanoma patient blood for unique cell surface markers among neutrophils. Markers were tested for their predictiveness using flow cytometry data and random forest machine learning.
We identified CD79b+ neutrophils (CD3-CD56-CD19-Siglec8-CD203c-CD86LoCD66b+CD79b+) that are normally restricted to the bone marrow in healthy humans but appear in the blood of subjects with early-stage melanoma. Further, we found CD79b+ neutrophils present in tumors of subjects with head and neck cancer. AI-mediated machine learning analysis of neutrophils from subjects with melanoma confirmed that CD79b expression among peripheral blood neutrophils is highly important in identifying melanoma incidence. We noted that CD79b+ neutrophils possessed a neutrophilic appearance but have transcriptional and surface-marker phenotypes reminiscent of B cells. Compared to remaining blood neutrophils, CD79b+ neutrophils are primed for NETosis, express higher levels of antigen presentation-related proteins, and have an increased capacity for phagocytosis.
Our work suggests that CD79b+ neutrophils are associated with early-stage melanoma.
Using mass cytometry, we profiled melanoma patient blood for unique cell surface markers among neutrophils. Markers were tested for their predictiveness using flow cytometry data and random forest machine learning.
We identified CD79b+ neutrophils (CD3-CD56-CD19-Siglec8-CD203c-CD86LoCD66b+CD79b+) that are normally restricted to the bone marrow in healthy humans but appear in the blood of subjects with early-stage melanoma. Further, we found CD79b+ neutrophils present in tumors of subjects with head and neck cancer. AI-mediated machine learning analysis of neutrophils from subjects with melanoma confirmed that CD79b expression among peripheral blood neutrophils is highly important in identifying melanoma incidence. We noted that CD79b+ neutrophils possessed a neutrophilic appearance but have transcriptional and surface-marker phenotypes reminiscent of B cells. Compared to remaining blood neutrophils, CD79b+ neutrophils are primed for NETosis, express higher levels of antigen presentation-related proteins, and have an increased capacity for phagocytosis.
Our work suggests that CD79b+ neutrophils are associated with early-stage melanoma.
摘要：
■由于它们在血液中的丰富，低RNA含量，而且寿命很短,嗜中性粒细胞通常被认为是一个同质池。然而,最近的研究发现,成熟的嗜中性粒细胞和嗜中性粒细胞祖细胞是由表现出环境依赖性功能的独特亚群组成.在这项研究中,我们询问中性粒细胞异质性是否与黑色素瘤发病率和/或疾病分期相关.
■使用质谱仪，我们对黑素瘤患者血液中的中性粒细胞中独特的细胞表面标志物进行了分析。使用流式细胞术数据和随机森林机器学习测试标记的预测性。
■我们鉴定了CD79b+嗜中性粒细胞(CD3-CD56-CD19-Siglec8-CD203c-CD86LoCD66b+CD79b+),其通常限于健康人的骨髓,但出现在患有早期黑色素瘤的受试者的血液中。Further,我们发现CD79b+中性粒细胞存在于头颈部癌患者的肿瘤中.来自黑素瘤受试者的嗜中性粒细胞的AI介导的机器学习分析证实,外周血嗜中性粒细胞中的CD79b表达在识别黑素瘤发病率中是非常重要的。我们注意到CD79b+中性粒细胞具有嗜中性的外观，但具有转录和表面标记表型，让人联想到B细胞。与剩余的血液中性粒细胞相比，CD79b+中性粒细胞为NETosis准备，表达更高水平的抗原呈递相关蛋白，并且具有增强的吞噬能力。
■我们的研究表明CD79b+中性粒细胞与早期黑色素瘤相关。
■使用质谱仪，我们对黑素瘤患者血液中的中性粒细胞中独特的细胞表面标志物进行了分析。使用流式细胞术数据和随机森林机器学习测试标记的预测性。
■我们鉴定了CD79b+嗜中性粒细胞(CD3-CD56-CD19-Siglec8-CD203c-CD86LoCD66b+CD79b+),其通常限于健康人的骨髓,但出现在患有早期黑色素瘤的受试者的血液中。Further,我们发现CD79b+中性粒细胞存在于头颈部癌患者的肿瘤中.来自黑素瘤受试者的嗜中性粒细胞的AI介导的机器学习分析证实,外周血嗜中性粒细胞中的CD79b表达在识别黑素瘤发病率中是非常重要的。我们注意到CD79b+中性粒细胞具有嗜中性的外观，但具有转录和表面标记表型，让人联想到B细胞。与剩余的血液中性粒细胞相比，CD79b+中性粒细胞为NETosis准备，表达更高水平的抗原呈递相关蛋白，并且具有增强的吞噬能力。
■我们的研究表明CD79b+中性粒细胞与早期黑色素瘤相关。
