# Integrated multi-omics, spatial profiling and organoid modeling drive transformative advances in chronic liver disease and hepatocellular carcinoma immunomicroenvironment research

## TL;DR

This paper reviews how new technologies are transforming the study of liver disease and liver cancer by combining detailed cell analysis, spatial mapping, and lab-grown liver models.

## Contribution

The paper introduces a synergistic integration of multi-omics, spatial transcriptomics, and organoid modeling to decode liver immunomicroenvironments.

## Key findings

- Single-cell sequencing reveals immune cell diversity and regulatory networks in chronic liver disease.
- Spatial transcriptomics maps immune-stromal interactions in liver structures like fibrotic septa and tumor niches.
- Organoid models replicate liver disease features for drug screening and personalized treatment exploration.

## Abstract

Chronic liver disease (CLD) represents a major global public health challenge, necessitating a systematic understanding of its complex immunopathological mechanisms. This review comprehensively summarizes the groundbreaking applications of cutting-edge technologies—including single-cell sequencing, spatial transcriptomics, and organoid models—in chronic liver disease immunology research: Single-cell sequencing resolves immune cell heterogeneity at unprecedented resolution, identifies rare cell subsets, and reveals dynamic changes and regulatory networks through multi-omics integration; Spatial transcriptomics complements this by mapping immune-stromal interactions within structural contexts such as the portal tract, fibrotic septa, and tumor niches, uncovering spatially organized immune evasion mechanisms and microenvironmental remodeling; Organoid technology constructs humanized liver-immune models that recapitulate disease-specific features—such as fibrosis, steatohepatitis, and hepatocellular carcinoma—enabling mechanistic validation, drug screening, and individualized therapeutic exploration. The synergistic integration of multi-omics profiling, spatial mapping, and organoid modeling is driving a paradigm shift in chronic liver disease immunology—transitioning from static cellular descriptions to spatiotemporal mechanism decoding, and from population-level insights to individualized pathophysiology and treatment prediction. These advanced approaches establish a technological foundation for building precision immunotherapeutic strategies tailored to spatiotemporal regulation of the liver immune microenvironment.