Cited by 683Immune cells in cancerSingle-cell and spatial transcriptomicsCancer Immunotherapy and Biomarkers

Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease

Open access
Mulder, Kevin, Patel, Amit Ashok, Kong, Wan Ting, Piot, Cécile, Halitzki, Evelyn, Dunsmore, Garett, Khalilnezhad, Shabnam, Irac, Sergio Erdal +24 more·2021·Immunity

Abstract

Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumor-associated macrophage populations. In particular, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumor periphery in a T cell-dependent manner via interferon-γ (IFN-γ) and CD40/CD40L-induced maturation from IFN-primed monocytes. IL4I1_Macs exhibited immunosuppressive characteristics through tryptophan degradation and promoted the entry of regulatory T cell into tumors. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.

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Crossref · 10.1016/j.immuni.2021.07.007

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Authors
Mulder, K., Patel, A. A., Kong, W. T., Piot, C., Halitzki, E., Dunsmore, G., Khalilnezhad, S., Irac, S. E., Dubuisson, A., Chevrier, M., Zhang, X. M., Tam, J. K. C., Lim, T. K. H., Wong, R. M. M., Pai, R., Khalil, A. I. S., Chow, P. K. H., Wu, S. Z., Al-Eryani, G., Roden, D., Swarbrick, A., Chan, J. K. Y., Albani, S., Derosa, L., Zitvogel, L., Sharma, A., Chen, J., Silvin, A., Bertoletti, A., Blériot, C., Dutertre, C.-A., & Ginhoux, F.
Affiliations
  • Inserm (FR)
  • Singapore Immunology Network (SG)
  • Agency for Science, Technology and Research (SG)
  • National University of Singapore (SG)
  • Singapore General Hospital (SG)
  • Nanyang Technological University (SG)
  • National Cancer Centre Singapore (SG)
  • Garvan Institute of Medical Research (AU)
  • Institut Gustave Roussy (FR)
  • Duke-NUS Medical School (SG)
Corresponding author
  • Dutertre, Charles-Antoine
  • Ginhoux, Florent
Venue
Immunity
Publisher
Elsevier BV
Published
2021-08
Volume
54
Issue
8
Pages
1883-1900.e5
ISSN
1074-7613 (ISSN-L)
OpenAlex
W3187504732
Cited by
678
References
85
Citations by year
2026: 137 · 2025: 168 · 2024: 162 · 2023: 128 · 2022: 77 · 2021: 6
FWCI
34.98
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • UWA Profiles and Research Repository (UWA) (submittedVersion)
  • National University of Singapore (submittedVersion)
  • DR-NTU (Nanyang Technological University) (submittedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
monocytes, macrophages, mononuclear phagocytes, tumor-associated macrophages, PD-L1, IDO1, IL4I1, interferon-gamma, CD40/CD40L, regulatory T cells, tryptophan degradation, tumor immunosuppression, inflammation, dendritic cells
MeSH terms
Tumor-Associated Macrophages, COVID-19, Arthritis, Rheumatoid, Dendritic Cells, Humans, Interferon-gamma, Liver Cirrhosis, Macrophages, Monocytes, Neoplasms, Gene Expression, RNA, Small Cytoplasmic, Gene Expression Profiling, T-Lymphocytes, Regulatory, L-Amino Acid Oxidase, Single-Cell Analysis, Transcriptome

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