THBS1 myeloid cells expand in SLD hepatocellular carcinoma and contribute to immunosuppression and unfavorable prognosis through TREM1.
Fiche publication
Date publication
février 2024
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier
Tous les auteurs :
Giraud J, Chalopin D, Ramel E, Boyer T, Zouine A, Derieppe MA, Larmonier N, Adotevi O, Le Bail B, Blanc JF, Laurent C, Chiche L, Derive M, Nikolski M, Saleh M
Lien Pubmed
Résumé
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 (M) cells expressing monocyte- and neutrophil-affiliated genes. THBS1 M cells expand in SLD-associated HCC, populate fibrotic lesions, and are associated with poor prognosis. THBS1 M 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.
Mots clés
CP: Cancer, TREM1, hepatocellular carcinoma, immunotherapy, inflammation, innate immunity, liver cancer, metabolism, myeloid cells, steatohepatitis
Référence
Cell Rep. 2024 02 12;:113773