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

Gustave Roussy Cancer Campus, Villejuif, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France; Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore. Gustave Roussy Cancer Campus, Villejuif, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France. Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore. Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore; Life and Medical Sciences Institute, University of Bonn, Bonn, Germany. Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore. Department of Pathology, Singapore General Hospital, 20 College Road, Singapore 169856, Singapore. Genome Institute of Singapore, A(∗)STAR, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore. Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore. Division of Surgical Oncology, National Cancer Centre, Singapore 169610, Singapore. The Kinghorn Cancer Centre and Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia. Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore; Academic Clinical Program in Obstetrics and Gynaecology, Duke-NUS Medical School, Singapore 169857, Singapore; Experimental Fetal Medicine Group, Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, Singapore 119228, Singapore; Program in Emerging Infectious Disease, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore. Translational Immunology Institute, SingHealth/Duke-NUS Academic Medical Centre, the Academia, 20 College Road, Discovery Tower Level 8, Singapore 169856, Singapore. Gustave Roussy Cancer Campus, Villejuif, France; Cancer Medicine Department, Gustave Roussy, Villejuif, France. Gustave Roussy Cancer Campus, Villejuif, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France; Cancer Medicine Department, Gustave Roussy, Villejuif, France; Université Paris-Saclay, Ile-de-France, France; Center of Clinical Investigations in Biotherapies of Cancer (BIOTHERIS), 1428 Villejuif, France. Genome Institute of Singapore, A(∗)STAR, 60 Biopolis Street, Genome, #02-01, Singapore 138672, Singapore; Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, the University of Western Australia, PO Box 7214, 6 Verdun Street, Nedlands, Perth, WA 6009, Australia; School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Institute, Curtin University, Perth, WA 6102, Australia. Program in Emerging Infectious Disease, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore. Gustave Roussy Cancer Campus, Villejuif, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France; Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore; Translational Immunology Institute, SingHealth/Duke-NUS Academic Medical Centre, the Academia, 20 College Road, Discovery Tower Level 8, Singapore 169856, Singapore. Electronic address: charles-antoine.dutertre@inserm.fr. Singapore Immunology Network (SIgN), A(∗)STAR, 8A Biomedical Grove, Immunos Building, Singapore 138648, Singapore; Translational Immunology Institute, SingHealth/Duke-NUS Academic Medical Centre, the Academia, 20 College Road, Discovery Tower Level 8, Singapore 169856, Singapore; Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: florent_ginhoux@immunol.a-star.edu.sg.

Immunity. 2021;(8):1883-1900.e5
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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.