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Immunity. 2019 May 21;50(5):1317-1334.e10. doi: 10.1016/j.immuni.2019.03.009. Epub 2019 Apr 9.

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

Author information

1
Department of Systems Biology, Harvard Medical School, Boston, MA, USA; Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
2
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.
3
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA.
4
Department of Systems Biology, Harvard Medical School, Boston, MA, USA; Precision Immunology, Immunology and Inflammation Therapeutic Area, Sanofi, US. Electronic address: virginia.savova@sanofi.com.
5
Graduate Program in Immunology, Harvard Medical School, Boston, MA, USA; Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
6
Pediatric Surgical Research Laboratories, Massachusetts General Hospital and Department of Surgery, Harvard Medical School, Boston, MA, USA.
7
Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA.
8
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.
9
Division of Thoracic Surgery, The Lung Center and the International Mesothelioma Program, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
10
Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA; Cancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore.
11
Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA. Electronic address: mpittet@mgh.harvard.edu.
12
Department of Systems Biology, Harvard Medical School, Boston, MA, USA. Electronic address: allon_klein@hms.harvard.edu.

Abstract

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.

KEYWORDS:

dendritic cell heterogeneity; macrophage heterogeneity; mouse-human comparison; myeloid cells; neutrophil heterogeneity; single-cell analysis; tumor immunology; tumor microenvironment

PMID:
30979687
PMCID:
PMC6620049
[Available on 2020-05-21]
DOI:
10.1016/j.immuni.2019.03.009
[Indexed for MEDLINE]

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