Multi-omics Identifies Tumor-Intrinsic SREBP1 Driving Immune Exclusion in Hepatocellular Carcinoma

Immune checkpoint inhibitors (ICI) have improved patient outcomes in hepatocellular carcinoma (HCC); however most patients do not experience durable benefit. The non-T cell-inflamed tumor microenvironment (TME), characterized by limited CD8+ T cell infiltration, reduced dendritic cell function, and low IFNγ-associated gene expression, is associated with lower likelihood of response to ICI. To nominate new therapeutic targets for overcoming ICI resistance in HCC, we conduced single cell RNAseq using 10X Genomics on 6 primary HCC tumors. Cells were isolated from HCC tumors using Millitenyi Gentle MACS digestion protocols and single cell suspensions were subjected to 5' 10X single cell RNAseq from 10X Genomics using 5' chemistry. Indicated samples were sequenced at the University of Pittsburgh Medical Center Genome Core or at Novogene (or both). We aimed for 50,000 reads/cell in an estimated 10,000 cells per sample. We utilized Cell Ranger software (v7.0) for alignment to the human reference sequence (GRCh38) *************************************************************** Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access. ***************************************************************