IFN-γ–driven immune networks in hepatocellular carcinoma

Year 2026, Volume: 8 Issue: 2, 324 - 330, 10.03.2026

Duygu Kırkık , Alpaslan Tanoğlu

https://doi.org/10.38053/acmj.1870749

https://izlik.org/JA97AS34JA

Abstract

Aims: The immune microenvironment of hepatocellular carcinoma (HCC) is complex and heterogeneous, limiting the efficacy of immune-based therapies. Interferon-gamma (IFN-γ) plays a pivotal role in antitumor immunity, regulating antigen presentation, immune cell recruitment, and cytotoxic effector functions. This study utilized integrated in-silico immunogenetic and immunoinformatic approaches to comprehensively characterize key components of the IFN-γ signaling axis in HCC.
Methods: Network analysis revealed a highly interconnected IFN-γ–centered immune module, driven by co-expression and encompassing antigen presentation, chemokine signaling, cytotoxic effector functions, and immune regulation. Functional enrichment analyses highlighted immune pathways related to cytokine signaling, antigen processing, and natural killer cell cytotoxicity. The Interferome database confirmed consistent IFN-γ–responsive transcriptional patterns across multiple biological contexts, validating the IFN-γ responsiveness of selected genes.
Results: Epitope prediction identified multiple high-affinity CD8⁺ T-cell epitopes derived from STAT1, CXCL10, GZMB, and IDO1, with broad HLA class I binding capacity. These findings define IFN-γ signaling in HCC as an integrated immune network with immunogenetic relevance, supporting its potential utility for immune-based stratification and the development of rational immunotherapeutic strategies. The characterization of the IFN-γ signaling axis in HCC provides valuable insights into the complex interactions between immune cells and tumor cells, highlighting the importance of IFN-γ in shaping the immune microenvironment.
Conclusion: The study's results have significant implications for the development of effective immunotherapies for HCC, suggesting that targeting the IFN-γ signaling axis may enhance antitumor immunity and improve treatment outcomes. Further research is needed to explore the clinical applications of these findings and to develop novel immunotherapeutic strategies that harness the power of IFN-γ to combat HCC. By elucidating the complex interactions within the IFN-γ signaling axis, this study contributes to a deeper understanding of the immune microenvironment in HCC.

Keywords

Interferon-gamma , hepatocellular carcinoma , immunogenetics , CD8⁺ T-cell epitopes , HLA class I

Ethical Statement

This study was conducted using publicly available datasets and in silico analytical approaches. No human participants or animals were directly involved in the study. Therefore, ethical committee approval and informed consent were not required.

Supporting Institution

N/A

Thanks

N/A

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