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Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease
Open accessAbstract
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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“Considering that the functional diversity of macrophages during polarization have recently been reported36,61, our arguments need to be further validated by using single-cell phenotypic analysis, which will allow us to delineate the heterogeneity of infiltrating”
From Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation (2023) · cites this paper as [61]
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Voigt, A. P., Mullin, N. K., Mulfaul, K., Lozano, L. P., Wiley, L. A., Flamme‐Wiese, M. J., Boese, E. A., Han, I. C., Scheetz, T. E., Stone, E. M., et al. (2022) · Human Molecular Genetics · doi:10.1093/hmg/ddac043 · Cited by 64
FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice
Momenilandi, M., Lévy, R., Sobrino, S., Li, J., Lagresle‐Peyrou, C., Esmaeilzadeh, H., Fayand, A., Floc’h, C. L., Guérin, A., Mina, E. D., et al. (2024) · Cell · doi:10.1016/j.cell.2024.04.009 · Cited by 66
Self-citationMacDonald, L., Elmesmari, A., Somma, D., Frew, J., Mario, C. D., Madhu, R., Paoletti, A., Simakou, T., Hardy, O. M., Tolusso, B., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.11.004 · Cited by 69
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Defining and using immune archetypes to classify and treat cancer
Combes, A. J., Samad, B., & Krummel, M. F. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00578-2 · Cited by 61
Monocyte differentiation within tissues: a renewed outlook
Rigamonti, A., Villar, J., & Segura, É. (2023) · Trends in Immunology · doi:10.1016/j.it.2023.10.005 · Cited by 66
The spatial and temporal activation of macrophages during fibrosis
Behmoaras, J. V., Mulder, K., Ginhoux, F., & Petretto, E. G. (2025) · Nature reviews. Immunology · doi:10.1038/s41577-025-01186-x · Cited by 75
Self-citationExploring the Impact of TREM2 in Tumor-Associated Macrophages
Khantakova, D., Brioschi, S., & Molgora, M. (2022) · Vaccines · doi:10.3390/vaccines10060943 · Cited by 69
Guidelines for mouse and human DC generation
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Macrophage immunotherapy: overcoming impediments to realize promise
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Liang, X., Gao, H., Xiao, J. Y., Han, S., He, J., Yuan, R., Yang, S., & Yao, C. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1185985 · Cited by 59
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Sopa: a technology-invariant pipeline for analyses of image-based spatial omics
Blampey, Q., Mulder, K., Gardet, M., Christodoulidis, S., Dutertre, C., André, F., Ginhoux, F., & Cournède, P.-H. (2024) · Nature Communications · doi:10.1038/s41467-024-48981-z · Cited by 69
Self-citationMicroenvironmental determinants of endothelial cell heterogeneity
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Immunometabolism of tumor-associated macrophages: A therapeutic perspective
Karimova, A. F., Khalitova, A. R., Suezov, R. V., Markov, N., Mukhamedshina, Y. O., Rizvanov, A. A., Huber, M., Simon, H., & Brichkina, A. I. (2025) · European Journal of Cancer · doi:10.1016/j.ejca.2025.115332 · Cited by 65
Reprogramming of Hepatic Metabolism and Microenvironment in Nonalcoholic Steatohepatitis
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Self-citationThe roles of tissue resident macrophages in health and cancer
Cao, M., Wang, Z., Lan, W., Xiang, B., Liao, W., Zhou, J., Liu, X., Wang, Y., Zhang, S., Lu, S., et al. (2024) · Experimental Hematology and Oncology · doi:10.1186/s40164-023-00469-0 · Cited by 59
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CD116+ fetal precursors migrate to the perinatal lung and give rise to human alveolar macrophages
Evren, E., Ringqvist, E. E., Doisne, J., Thaller, A., Sleiers, N., Flavell, R. A., Santo, J. P. D., & Willinger, T. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20210987 · Cited by 60
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Crosstalk between tumor-associated macrophages and neighboring cells in hepatocellular carcinoma
Sung, P. S. (2021) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2021.0308 · Cited by 52
Metadata
- 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
- ORCID
- Mulder, Kevin
- Patel, Amit Ashok
- Kong, Wan Ting
- Piot, Cécile
- Halitzki, Evelyn
- Dunsmore, Garett
- Irac, Sergio Erdal
- Dubuisson, Agathe
- Zhang, Xiao Meng
- Tam, John Kit Chung
- Lim, Tony Kiat Hon
- Khalil, Ahmed Ibrahim Samir
- Chow, Pierce Kah Hoe
- Roden, Daniel
- Swarbrick, Alexander
- Chan, Jerry Kok Yen
- Albani, Salvatore
- Derosa, Lisa
- Zitvogel, Laurence
- Sharma, Ankur
- Chen, Jinmiao
- Silvin, Aymeric
- Bertoletti, Antonio
- Blériot, Camille
- 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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 374 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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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