Innate lymphoid cell heterogeneity and etiology-specific reprogramming in hepatocellular carcinoma - PubMed
3 months ago
- #Innate lymphoid cells
- #Tumor microenvironment
- #Hepatocellular carcinoma
- Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally.
- The study profiles innate lymphoid cells (ILCs) in HCC using scRNA-seq, bulk RNA-seq, and CyTOF from 50 patients with different etiologies (HBV and non-viral).
- ILC1 subsets were identified as proliferative (ILC1p) and cytotoxic (ILC1c), while ILC2 showed type-2 immune traits and ILC3 expressed key transcription factors and IL18.
- ILC subsets varied significantly by disease etiology, with NV-HCC ILC2s showing pro-fibrotic and tumor-promoting signatures.
- ILC1s in NV-HCC exhibited activated and cytotoxic phenotypes, whereas HBV-HCC ILC1s showed exhaustion markers like CD96 and TIGIT.
- NV-HCC ILC1s demonstrated enhanced IL-2/IL-15 signaling and interactions with CD8+ T cells via HLA-E, suggesting antitumor potential.
- The study highlights etiology-associated differences in ILC phenotypes and their roles in modulating immune responses in HCC.