Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species.,Immunity

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Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species.
Immunity ( IF 25.5 ) Pub Date : 2019-04-09 , DOI: 10.1016/j.immuni.2019.03.009
Rapolas Zilionis ₁ , Camilla Engblom ₂ , Christina Pfirschke ₃ , Virginia Savova ₄ , David Zemmour ₅ , Hatice D Saatcioglu ₆ , Indira Krishnan ₇ , Giorgia Maroni ₈ , Claire V Meyerovitz ₉ , Clara M Kerwin ₉ , Sun Choi ₉ , William G Richards ₉ , Assunta De Rienzo ₉ , Daniel G Tenen ₁₀ , Raphael Bueno ₉ , Elena Levantini ₈ , Mikael J Pittet ₃ , Allon M Klein ₁₁

Affiliation

Department of Systems Biology, Harvard Medical School, Boston, MA, USA; Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA; Graduate Program in Immunology, Harvard Medical School, Boston, MA, USA.
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.
Department of Systems Biology, Harvard Medical School, Boston, MA, USA; Precision Immunology, Immunology and Inflammation Therapeutic Area, Sanofi, US.
Graduate Program in Immunology, Harvard Medical School, Boston, MA, USA; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Pediatric Surgical Research Laboratories, Massachusetts General Hospital and Department of Surgery, Harvard Medical School, Boston, MA, USA.
Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA.
Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA; Institute of Biomedical Technologies, National Research Council (CNR), Pisa, Italy.
Division of Thoracic Surgery, The Lung Center and the International Mesothelioma Program, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA; Cancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore.
Department of Systems Biology, Harvard Medical School, Boston, MA, USA.

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.

中文翻译：

人类和小鼠肺癌的单细胞转录组学揭示了个体和物种之间保守的骨髓群体。

肿瘤浸润性髓样细胞（TIMs）包含单核细胞，巨噬细胞，树突状细胞和嗜中性粒细胞，并已成为癌症生长的关键调节剂。这些细胞可以多样化进入多种状态，这可能会促进或限制肿瘤的生长，但人们对此知之甚少。在这里，我们使用单细胞RNA测序（scRNA-seq）对非小细胞肺癌患者的TIMs进行定位。我们发现了25个TIM状态，其中大多数是在患者中可重复发现的。为了促进这些人群的翻译研究，我们还对小鼠中的TIMs进行了分析。在比较跨物种的TIMs时，我们发现树突状细胞和单核细胞之间的种群结构几乎完全一致。保守的中性粒细胞亚群；和巨噬细胞之间的物种差异。相比之下，患者体内的骨髓细胞群结构血液与TIM的重叠有限。这项研究确定了肺TIM的情况，并为将来研究TIM作为免疫治疗靶标的潜力奠定了基础。

更新日期：2019-04-09

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