Exploration of the Roles and Mechanisms Between Tumor-Infiltrating Lymphocytes and Hepatocellular Carcinoma Based on...

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Hepatocellular carcinoma (HCC), particularly NASH-HCC, presents significant treatment challenges.
• The tumor immune microenvironment (TIME) and tumor-infiltrating lymphocytes (TILs) are critical in HCC progression and treatment response.

Purpose of the Study:

• To investigate the immunosuppressive role of TIL-related genes in NASH-HCC.
• To identify potential prognostic factors for NASH-HCC.
• To explore therapeutic strategies targeting the TIME.

Main Methods:

• Gene Set Enrichment Analysis (GSEA) and Weighted Gene Coexpression Network Analysis (WGCNA) were used to analyze immune suppression and identify gene modules.
• Machine learning models were developed for prognostic prediction and validated using GEO and TCGA datasets.
• Single-cell RNA sequencing (scRNA-seq) analyzed TIL-related gene roles in distinct immune cell populations.

Main Results:

• 10 distinct cell types were identified in HCC, with T cells showing the highest TIL pathway activity.
• TILs were found to play a critical role in cellular communication through MIF signaling.
• A prognostic model based on TIL-related genes demonstrated predictive power.

Conclusions:

• TILs exhibit an immunosuppressive function in NASH-HCC.
• TIL-related genes are significant independent prognostic factors for NASH-HCC.
• These findings offer insights for developing novel immunotherapeutic strategies for NASH-HCC.