University of Bordeaux Animal Facilites, 33600 Pessac, France
Nicolas Larmonier
University of Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, 33000 Bordeaux, France
Olivier Adotevi
Université Bourgogne Franche-Comté, INSERM, UMR1098, 25000 Besançon, France
Brigitte Le Bail
Bordeaux University Hospital, Division of Pathology, Pellegrin Hospital, 33000 Bordeaux, France
Jean-Frédéric Blanc
University of Bordeaux Hospital, Division of Gastrohepatology and Oncology, Haut Leveque Hospital, 33604 Pessac, France
Christophe Laurent
University of Bordeaux Hospital, Division of Gastrohepatology and Oncology, Haut Leveque Hospital, 33604 Pessac, France
Laurence Chiche
University of Bordeaux Hospital, Division of Gastrohepatology and Oncology, Haut Leveque Hospital, 33604 Pessac, France
Marc Derive
Inotrem SA, Nancy, France
Macha Nikolski
University of Bordeaux, CNRS, IBGC, UMR 5095, 33000 Bordeaux, France
Maya Saleh
University of Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, 33000 Bordeaux, France; Institut National de la Recherche Scientifique (INRS), Armand Frappier Health & Biotechnology (AFSB) Research Center, Laval, QC H7V 1B7, Canada; Corresponding author
Summary: Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral or non-viral etiologies including steatotic liver diseases (SLDs). Expansion of immunosuppressive myeloid cells is a hallmark of inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance. Here, we present a high-resolution atlas of innate immune cells from patients with HCC that unravels an SLD-associated contexture characterized by influx of inflammatory and immunosuppressive myeloid cells, including a discrete population of THBS1+ regulatory myeloid (Mreg) cells expressing monocyte- and neutrophil-affiliated genes. THBS1+ Mreg cells expand in SLD-associated HCC, populate fibrotic lesions, and are associated with poor prognosis. THBS1+ Mreg cells are CD163+ but distinguished from macrophages by high expression of triggering receptor expressed on myeloid cells 1 (TREM1), which contributes to their immunosuppressive activity and promotes HCC tumor growth in vivo. Our data support myeloid subset-targeted immunotherapies to treat HCC.
