Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species
Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species
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DOI：
10.1016/j.immuni.2019.03.009
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发表时间：
2019-05-21
期刊：
影响因子：
32.4
通讯作者：
Klein, Allon M.
中科院分区：
文献类型：
--
作者：
Zilionis, Rapolas;Engblom, Camilla;Klein, Allon M.
肿瘤浸润性骨髓细胞（TIM）包括单核细胞、巨噬细胞、树突状细胞和嗜中性粒细胞，并且已经成为癌症生长的关键调节因子。这些细胞可以分化成一系列状态，这些状态可能促进或限制肿瘤生长，但仍然知之甚少。在这里，我们使用单细胞RNA测序（scRNA-seq）来绘制非小细胞肺癌患者的TIM。我们发现了25种TIM状态，其中大多数在患者中可重复发现。为了促进这些群体的转化研究，我们还分析了小鼠中的TIM。在比较不同物种的TIM时，我们发现树突状细胞和单核细胞之间的群体结构几乎完全一致;保守的中性粒细胞亚群;以及巨噬细胞之间的物种差异。相比之下，患者血液中的骨髓细胞群体结构与TIM的重叠有限。这项研究确定了肺部TIM的前景，并为未来研究TIM作为免疫治疗靶点的潜力奠定了基础。
Tumor-infiltrating myeloid cells (TIMs) comprise monocytes, macrophages, dendritic cells, and neutrophils, and have emerged as key regulators of cancer growth. These cells can diversify into a spectrum of states, which might promote or limit tumor outgrowth but remain poorly understood. Here, we used single-cell RNA sequencing (scRNA-seq) to map TIMs in non-small-cell lung cancer patients. We uncovered 25 TIM states, most of which were reproducibly found across patients. To facilitate translational research of these populations, we also profiled TIMs in mice. In comparing TIMs across species, we identified a near-complete congruence of population structures among dendritic cells and monocytes; conserved neutrophil subsets; and species differences among macrophages. By contrast, myeloid cell population structures in patients' blood showed limited overlap with those of TIMs. This study determines the lung TIM landscape and sets the stage for future investigations into the potential of TIMs as immunotherapy targets.