Identification of TREM1+CD163+ myeloid cells as a deleterious immune subset in HCC [Spatial Transcriptomics]

Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral and non-viral etiologies. Expansion of suppressive myeloid cells is a hallmark of chronic inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance in the steatohepatitis setting. Here, we present a high resolution atlas of hepatic innate immune cells from patients with HCC that unravels a steatohepatitis contexture characterized by influx of inflammatory and immunosuppressive myeloid cells. A discrete myeloid cell population identified by selective expression of TREM1 and CD163 expands in steatohepatitis-HCC. We refer to this population as TREM1+ regulatory myeloid cells (Mreg), as it potently suppresses T cell effector functions, highly expresses TGFB1 and IL13RA1 and localizes to HCC fibrotic lesions. Single-cell RNA-seq (10x Genomics) on FACS-sorted CD45 + panTCRαβ - CD19 - innate immune cells freshly isolated from tumors (HCC) and adjacent non-tumoral (NT) liver sections were realized for 10 patients (10 HCC/CHC samples and 10 NT/TS samples). In parallel, we applied spatial transcriptomics (ST; Visium ® , 10x Genomics) on frozen tissue sections from two of the previous patients (2 CHC visium samples). Furthermore, bulk RNA-seq sequencing were performed on innate immunity cells that were isolated using the same sorting strategy designed for scRNAseq experiments, for six of the previous patients. Bulk RNA-seq sequencing were also realized on FACS-sorted cell population, namely THBS1_M (c0, c3 and c4) populations that were isolated according to specific sorting strategy. In summary, available data concerns 20 scRNA-seq samples, 2 visium spatial transcriptomics and 9 bulk RNA-seq.