THBS1+ myeloid cells expand in SLD hepatocellular carcinoma and contribute to immunosuppression and unfavorable prognosis through TREM1

Giraud, Julie; Chalopin, Domitille; Ramel, Eloïse; Boyer, Thomas; Zouine, Atika; Derieppe, Marie-Alix; Larmonier, Nicolas; Adotevi, Olivier; Le Bail, Brigitte; Blanc, Jean-Frédéric; Laurent, Christophe; Chiche, Laurence; Derive, Marc; Nikolski, Macha et Saleh, Maya ORCID: https://orcid.org/0000-0003-1538-9146 (2024). THBS1+ myeloid cells expand in SLD hepatocellular carcinoma and contribute to immunosuppression and unfavorable prognosis through TREM1 Cell Reports , vol. 43 , nº 113773. pp. 1-25. DOI: 10.1016/j.celrep.2024.113773.

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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 (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.

Type de document:	Article
Mots-clés libres:	CP: Cancer; TREM1; hepatocellular carcinoma; immunotherapy; inflammation; innate immunity; liver cancer; metabolism; myeloid cells; steatohepatitis
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	27 févr. 2024 19:28
Dernière modification:	27 févr. 2024 19:28
URI:	https://espace.inrs.ca/id/eprint/14333

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