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Single-Cell Transcriptomic Atlas of Human Hepatic ILCs Reveals the Enrichment of ILC2 in Liver Cancer

ABSTRACT: Here, we show the scRNA-seq-based analysis of 9 ILC samples sorted by flow cytometry, from blood, healthy livers, hepatocellular carcinoma (HCC) tumors, and HCC tumor-adjacent liver tissues. Unbiased transcriptional clustering revealed seven distinct ILC subpopulations in healthy liver and six in liver cancer, among which there were two tissue-resident NK cell subpopulations (CXCR6+CD16+ and CXCR6+CD16-) in healthy liver but only one tissue-resident NK cell subpopulation (CXCR6+CD16-) in tumor tissues. Notably, ILC2s were significantly accumulated in the HCC tissues, and bulk RNA sequencing of SLAMF1+ ILC2s and SLAMF1- ILC2s identified their function.

ORGANISM(S): Homo sapiens

PROVIDER: GSE162616 | GEO | 2022/09/26

REPOSITORIES: GEO

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Comparison of Eomes-negative and Eomes-positive human liver NK cells by RNASeq

Project description:We sorted Eomes-negative NK cells (CD3- CD56+ CXCR6- CD16-) and Eomes-positive NK cells (CD3- CD56+ CXCR6+) from total leukocytes isolated from the perfusion fluid of five healthy human livers destined for transplantation. Total RNA was extracted from sorted cells, cDNA generated and RNASeq performed.

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The Tumor Microenvironment Shapes Innate Lymphoid Cells in Patients with Hepatocellular Carcinoma

Project description:Objective: Hepatocellular carcinoma (HCC) represents a typical inflammation-associated cancer. Tissue resident innate lymphoid cells (ILCs) have been suggested to control tumor surveillance. Here we studied how the local cytokine milieu controls ILCs in HCC. Design: We performed bulk RNA sequencing of HCC tissue as well as flow cytometry and single-cell RNA sequencing of enriched ILCs from non-tumor liver, margin and tumor core derived from 48 HCC patients. Simultaneous measurement of protein and RNA expression at the single-cell level (AbSeq) identified precise signatures of ILC subgroups. In-vitro culturing of ILCs was used to validate findings from in-silico analysis. Analysis of RNA-sequencing data from large HCC cohorts allowed stratification and survival analysis based on transcriptomic signatures. Results: RNA sequencing of tumor, non-tumor and margin identified tumor-dependent gradients of which were not only associated with poor survival but also control ILC plasticity. Single-cell RNA sequencing and flow cytometry of ILCs from HCC livers identified NK-like cells in the non-tumor tissue, losing their cytotoxic profile as they transitioned into tumor ILC1 and NK-like-ILC3 cells. Tumor ILC composition was mediated by cytokine gradients that directed ILC plasticity towards activated tumor ILC2s. This was liver-specific and not seen in ILCs from PBMC. Patients with high ILC2/ILC1 ratio expressed IL-33 in the tumor that promoted ILC2 generation which was associated with better survival. Conclusion: Our results suggest that the tumor cytokine milieu controls ILC composition and HCC outcome. Specific changes of cytokines modify ILC composition in the tumor by inducing plasticity and alter ILC function.

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The Tumor Microenvironment Shapes Innate Lymphoid Cells in Patients with Hepatocellular Carcinoma

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RNA-sequencing of Group 1, Group 2 and Group 3 ILCs used for Hi-C

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Energy metabolism and cell motility defect in NK-cells from patients with Hepatocellular Carcinoma

Project description:Natural Killer (NK) cells play a central role in cell-mediated immune response to cancer. In previous studies number and function of NK-cells have been shown to be positively correlated with HCC outcome. In this study, we have performed a genetic expression analysis comparing mRNA expression by NK cells from HCC patients to patients with the pre-neoplastic condition of liver cirrhosis and to healthy donors. The bioinformatic analysis has been completed by an immunophenotypic study and functional analysis of the main NK cell functions. It is known that NK cells may present functional defects in HCC patients however previous studies have not systematically address the molecular mechanisms associated with these defects by an unbiased genetic expression study. We could identify altered cellular pathways and hypothesize possible mechanisms that could be targeted for restoring an immune-protective NK cell response. NK cells were isolated and sorted from Hepatitis C virus (HCV)-related liver cirrhosis (10 patients), early stage HCC and HCV-related liver cirrhosis (14 patients) and seven healthy donors. RNA from sorted NK cells was processed, labeled and hybridized to Agilent microarrays.

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2023-03-11 | PXD026822 | Pride

Checkpoint Inhibitors Modulate Plasticity of Innate Lymphoid Cells in Peripheral Blood of Patients with Hepatocellular Carcinoma

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