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

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

Blog Article

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 Spacecraft 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 Grinders 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.