Study: Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species 70712 cells

This SCP study enables exploration of scRNAseq data published here.

Data also available on GEO.

 

Rapolas Zilionis,1,2,14 Camilla Engblom,3,4,14 Christina Pfirschke,3,14 Virginia Savova,1,5,14,* David Zemmour,4,6, Hatice D. Saatcioglu,7 Indira Krishnan,8,9 Giorgia Maroni,8,9,10 Claire V. Meyerovitz,11 Clara M., Kerwin,11 Sun Choi,11 William G. Richards,11 Assunta De Rienzo,11 Daniel G. Tenen,8,12 Raphael Bueno,11 Elena Levantini,8,9,10, Mikael J. Pittet,3,13,* and Allon M. Klein1,13,15,*


1Department of Systems Biology, Harvard Medical School, Boston, MA, USA
2Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania
3Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, MA, USA 4Graduate Program in Immunology, Harvard Medical School, Boston, MA, USA
5Precision Immunology, Immunology and Inflammation Therapeutic Area, Sanofi, US
6Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA
7Pediatric Surgical Research Laboratories, Massachusetts General Hospital and Department of Surgery, Harvard Medical School,
Boston, MA, USA
8Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA
9Beth Israel Deaconess Medical Center, Boston, MA, USA
10Institute of Biomedical Technologies, National Research Council (CNR), Pisa, Italy
11Division of Thoracic Surgery, The Lung Center and the International Mesothelioma Program, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
12Cancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore
13These authors contributed equally
14These authors contributed equally
15Lead Contact
*Correspondence: mpittet@mgh.harvard.edu (M.J.P.), virginia.savova@sanofi.com (V.S.), allon_klein@hms.harvard.edu (A.M.K.) https://doi.org/10.1016/j.immuni.2019.03.009

 

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 under- stood. 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 popula- tion structures among dendritic cells and mono- cytes; 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 land- scape and sets the stage for future investigations into the potential of TIMs as immunotherapy targets.