Research Article

IFN-γ–driven immune networks in hepatocellular carcinoma

Volume: 8 Number: 2 March 10, 2026

IFN-γ–driven immune networks in hepatocellular carcinoma

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

Supporting Institution

N/A

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.

Thanks

N/A

References

  1. Abboud Y, Ismail M, Khan H, et al. Hepatocellular carcinoma incidence and mortality in the USA by sex, age, and race: a nationwide analysis of two decades. J Clin Transl Hepatol. 2024;12(2):172-181. doi:10.14218/JC TH.2023.00356
  2. Altekruse SF, Henley SJ, Cucinelli JE, McGlynn KA. Changing hepatocellular carcinoma incidence and liver cancer mortality rates in the United States. Am J Gastroenterol. 2014;109(4):542-553. doi:10.1038/ajg.2014.11
  3. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30. doi:10.3322/caac.21166
  4. Bosch FX, Ribes J, Díaz M, Cléries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004;127(5 Suppl 1):S5-S16. doi: 10.1053/j.gastro.2004.09.011
  5. El-Serag HB, Mason AC. Risk factors for the rising rates of primary liver cancer in the United States. Arch Intern Med. 2000;160(21):3227-3230. doi:10.1001/archinte.160.21.3227
  6. Alqahtani A, Khan Z, Alloghbi A, Said Ahmed TS, Ashraf M, Hammouda DM. Hepatocellular carcinoma: molecular mechanisms and targeted therapies. Medicina (Kaunas). 2019;55(9):526. doi:10.3390/medicina55090526
  7. Yang YM, Kim SY, Seki E. Inflammation and liver cancer: molecular mechanisms and therapeutic targets. Semin Liver Dis. 2019;39(1):26-42. doi:10.1055/s-0038-1676806
  8. Chu YJ, Yang HI, Wu HC, et al. Aflatoxin B1 exposure increases the risk of hepatocellular carcinoma associated with hepatitis C virus infection or alcohol consumption. Eur J Cancer. 2018;94:37-46. doi:10.1016/j.ejca. 2018.02.010

Details

Primary Language

English

Subjects

Innate Immunity, Immunogenetics, Basic Immunology

Journal Section

Research Article

Publication Date

March 10, 2026

Submission Date

January 24, 2026

Acceptance Date

February 21, 2026

Published in Issue

Year 2026 Volume: 8 Number: 2

APA
Kırkık, D., & Tanoğlu, A. (2026). IFN-γ–driven immune networks in hepatocellular carcinoma. Anatolian Current Medical Journal, 8(2), 324-330. https://doi.org/10.38053/acmj.1870749
AMA
1.Kırkık D, Tanoğlu A. IFN-γ–driven immune networks in hepatocellular carcinoma. Anatolian Curr Med J / ACMJ / acmj. 2026;8(2):324-330. doi:10.38053/acmj.1870749
Chicago
Kırkık, Duygu, and Alpaslan Tanoğlu. 2026. “IFN-γ–driven Immune Networks in Hepatocellular Carcinoma”. Anatolian Current Medical Journal 8 (2): 324-30. https://doi.org/10.38053/acmj.1870749.
EndNote
Kırkık D, Tanoğlu A (March 1, 2026) IFN-γ–driven immune networks in hepatocellular carcinoma. Anatolian Current Medical Journal 8 2 324–330.
IEEE
[1]D. Kırkık and A. Tanoğlu, “IFN-γ–driven immune networks in hepatocellular carcinoma”, Anatolian Curr Med J / ACMJ / acmj, vol. 8, no. 2, pp. 324–330, Mar. 2026, doi: 10.38053/acmj.1870749.
ISNAD
Kırkık, Duygu - Tanoğlu, Alpaslan. “IFN-γ–driven Immune Networks in Hepatocellular Carcinoma”. Anatolian Current Medical Journal 8/2 (March 1, 2026): 324-330. https://doi.org/10.38053/acmj.1870749.
JAMA
1.Kırkık D, Tanoğlu A. IFN-γ–driven immune networks in hepatocellular carcinoma. Anatolian Curr Med J / ACMJ / acmj. 2026;8:324–330.
MLA
Kırkık, Duygu, and Alpaslan Tanoğlu. “IFN-γ–driven Immune Networks in Hepatocellular Carcinoma”. Anatolian Current Medical Journal, vol. 8, no. 2, Mar. 2026, pp. 324-30, doi:10.38053/acmj.1870749.
Vancouver
1.Duygu Kırkık, Alpaslan Tanoğlu. IFN-γ–driven immune networks in hepatocellular carcinoma. Anatolian Curr Med J / ACMJ / acmj. 2026 Mar. 1;8(2):324-30. doi:10.38053/acmj.1870749

 

TR DİZİN ULAKBİM and International Indexes (1b)
 

Interuniversity Board (UAK) Equivalency:  Article published in Ulakbim TR Index journal [10 POINTS], and Article published in other (excuding 1a, b, c) international indexed journal (1d) [5 POINTS]

Note: Our journal is not WOS indexed and therefore is not classified as Q.

You can download Council of Higher Education (CoHG) [Yüksek Öğretim Kurumu (YÖK)] Criteria) decisions about predatory/questionable journals and the author's clarification text and journal charge policy from your browser. https://dergipark.org.tr/tr/journal/3449/file/4924/show

 

Journal Indexes and Platforms: 

TR Dizin ULAKBİM, Google Scholar, Crossref, Worldcat (OCLC), DRJI, EuroPub, OpenAIRE, Turkiye Citation Index, Turk Medline, ROAD, ICI World of Journal's, Index Copernicus, ASOS Index, General Impact Factor, Scilit.


 

The indexes of the journal's are;


 

download?token=eyJhdXRoX3JvbGVzIjpbXSwiZW5kcG9pbnQiOiJqb3VybmFsIiwib3JpZ2luYWxuYW1lIjoiVHJfSW5kZXhfbG9nby5wbmciLCJwYXRoIjoiMDFiOS82MmZhLzA3MzMvNjlkZjNlNTdhMmI4ZjkuODYxMzMxMjQucG5nIiwiZXhwIjoxNzc2MjQxNzY3LCJub25jZSI6ImQyMTQ4MjdiNTg1ZjVmMGQwYzAzZTMxNzMwM2QwMThmIn0.RmnGvwR536HdIoKpGO-ApytZ5aRPRT_BFXE2EpGSIqc

asos-index.png
 
f9ab67f.png
 
WorldCat_Logo_H_Color.png
 

 

18596download?token=eyJhdXRoX3JvbGVzIjpbXSwiZW5kcG9pbnQiOiJqb3VybmFsIiwib3JpZ2luYWxuYW1lIjoiT3BlbkFpcmUuanBnIiwicGF0aCI6IjUyMWYvZjljYy8wMDk3LzY5ZGYzZDNiYmVkZGU0LjQzNDM2OTU3LmpwZyIsImV4cCI6MTc3NjI0MTQ4NCwibm9uY2UiOiIwYjgxZDE2NzRiNzhjMWQyOGVmMDM1OTA1MzI5NjdjZiJ9.xeFppR1ubA4i-dHG-u07ht9bQNogFheXQjLyEaP9GgAimages?q=tbn:ANd9GcQgDnBwx0yUPRKuetgIurtELxYERFv20CPAUcPe4jYrrJiwXzac8rGXlzd57gl8iikb1Tk&usqp=CAU

 

84039476_619085835534619_7808805634291269632_n.jpg

 

 

 

The platforms of the journal's are;
 

COPE.jpg
 
images?q=tbn:ANd9GcTbq2FM8NTdXECzlOUCeKQ1dvrISFL-LhxhC7zy1ZQeJk-GGKSx2XkWQvrsHxcfhtfHWxM&usqp=CAUicmje_1_orig.png
 
 
ncbi.png
 
ORCID_logo.pngimages?q=tbn:ANd9GcQlwX77nfpy3Bu9mpMBZa0miWT2sRt2zjAPJKg2V69ODTrjZM1nT1BbhWzTVPsTNKJMZzQ&usqp=CAU
 

 

images?q=tbn:ANd9GcTaWSousoprPWGwE-qxwxGH2y0ByZ_zdLMN-Oq93MsZpBVFOTfxi9uXV7tdr39qvyE-U0I&usqp=CAU
 


 


 

 


 


The indexes/platforms of the journal are;
 

TR Dizin Ulakbim, Crossref (DOI), Google Scholar, EuroPub, Directory of Research Journal İndexing (DRJI), Worldcat (OCLC), OpenAIRE, ASOS Index, ROAD, Turkiye Citation Index, ICI World of Journal's, Index Copernicus, Turk Medline, General Impact Factor, Scilit 
 


Journal articles are evaluated as "Double-Blind Peer Review"

 

All articles published in this journal are licensed under a Creative Commons Attribution 4.0 International License (CC BY NC ND)