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

• Published in: Immunity (Cambridge, Mass.) Vol. 50; no. 5; pp. 1317 - 1334.e10
• Main Authors: Zilionis, Rapolas, Engblom, Camilla, Pfirschke, Christina, Savova, Virginia, Zemmour, David, Saatcioglu, Hatice D., Krishnan, Indira, Maroni, Giorgia, Meyerovitz, Claire V., Kerwin, Clara M., Choi, Sun, Richards, William G., De Rienzo, Assunta, Tenen, Daniel G., Bueno, Raphael, Levantini, Elena, Pittet, Mikael J., Klein, Allon M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.05.2019; Elsevier Limited
• Subjects: Animals; Base Sequence; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line, Tumor; Collaboration; dendritic cell heterogeneity; Dendritic cells; Dendritic Cells - immunology; Dendritic structure; Experiments; Gene expression; Gene Expression Profiling; Gene sequencing; Grants; Granulocytes; Histology; Humans; Immunotherapy; Laboratory animals; Leukocytes (neutrophilic); Lung - immunology; Lung - pathology; Lung cancer; Lung Neoplasms - immunology; Lung Neoplasms - pathology; macrophage heterogeneity; Macrophages; Macrophages - immunology; Male; Mice; Mice, Inbred C57BL; Monocytes; Monocytes - immunology; mouse-human comparison; Myeloid cells; neutrophil heterogeneity; Neutrophils; Neutrophils - immunology; Patients; Populations; Regulators; Ribonucleic acid; RNA; Sequence Analysis, RNA; single-cell analysis; Species; Studies; tumor immunology; tumor microenvironment; Tumors; Singapore; macrophage heterogeneity; tumor immunology; myeloid cells; neutrophil heterogeneity; dendritic cell heterogeneity; mouse-human comparison; tumor microenvironment; single-cell analysis
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 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 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. [Display omitted] •Human dendritic cell and monocyte subsets show one-to-one equivalence in mouse•Neutrophils exhibit tumor-associated phenotypes that are conserved across species•Myeloid subsets in patient blood only partially overlap with those in their tumors•Unique markers define myeloid cell subsets and associate with clinical prognosis Tumor-infiltrating myeloid cells (TIMs) have emerged as key cancer regulators and potential next-generation immunotherapy targets, yet they remain incompletely understood. Using scRNA-seq, Zilionis et al. map the TIM landscape in human and murine lung tumors and systematically compare cell states, revealing conserved myeloid populations across individuals and species.