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Updated: Jun 25, 2025
Author Spotlight: Investigating Immune Cell Dynamics in the Tumor Microenvironment — Challenges and Innovations in Cancer Prognosis
Published on: April 12, 2024
Single-cell profiling reveals the metastasis-associated immune signature of hepatocellular carcinoma
Deyuan Zhong1,2, Ying Shi2, Wenzhe Ma3
1Liver Transplantation Center and HBP Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
Metastasis in hepatocellular carcinoma (HCC) is linked to a suppressive immune microenvironment. Key findings include enriched effector regulatory T cells (eTregs) and altered dendritic cells (DCs), offering new therapeutic targets for advanced HCC.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Metastasis is the primary cause of mortality in hepatocellular carcinoma (HCC).
- Understanding the immune microenvironment associated with HCC metastasis is crucial for developing effective treatments.
- The metastasis-associated immune signature in HCC warrants detailed exploration.
Purpose of the Study:
- To explore the metastasis-associated immune signature in hepatocellular carcinoma (HCC).
- To identify key immune cell populations and molecular markers associated with HCC metastasis.
- To uncover potential immune therapeutic targets for advanced HCC.
Main Methods:
- Bioinformatic analysis of single-cell transcriptome data from HCC patients.
- Analysis of cellular composition, pseudotime state transitions, and cell-cell interactions.
- Verification of identified genes and cell clusters.
Main Results:
- HCC with metastasis showed a suppressive immune microenvironment compared to HCC without metastasis.
- Effector regulatory T cells (eTregs) were enriched in metastatic HCC, with PHLDA1 identified as an exhaustion-specific gene linked to worse prognosis.
- A novel cluster of CCR7+ dendritic cells (DCs) with inhibited differentiation and impaired CCR7/CCL19 interaction was identified in metastatic HCC.
Conclusions:
- Metastatic HCC exhibits an upregulation of eTreg exhaustion-specific genes and an inhibition of CCL signaling in a novel DC cluster.
- These findings provide new insights into the immune landscape of advanced HCC.
- The identified immune alterations represent potential novel therapeutic targets for advanced HCC.
