AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025290309
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ORIGINAL RESEARCH ARTICLE

Effect of γδT-cell infiltration on the prognosis of hepatocellular carcinoma

Shiwei Xie1,2 ,  Erqiang Wang3 ,  Xia Zhao1 ,  Lihua Rong1,2 ,  Shuai Hu1,2 ,  Yufei Ge1,2 ,  Gang Xu1,2 ,  Zhi Xu1,2 ,  Yiming Fan1,2 ,  Yuchen Wang1,2 ,  Yumeng Zhang1,2 ,  Jiang Li1,2* ,  Shijie Zhang1,2*
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1 Department of General Surgery, The First Affiliated Hospital, Shihezi University, Shihezi, Xinjiang, China
2 The Department of Hepatobiliary Surgery, The First Affiliated Hospital of Shihezi University, Shihezi, Xinjiang, China
3 Department of Immunology, School of Basic Medicine of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
EJMO, 025290309 https://doi.org/10.36922/EJMO025290309
Received: 14 July 2025 | Revised: 16 September 2025 | Accepted: 4 November 2025 | Published online: 24 December 2025
(This article belongs to the Special Issue Tumor Immune Microenvironment and Intervention Strategies)
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Hepatocellular carcinoma (HCC) is a major cause of cancer death in China, linked to hepatitis, alcohol abuse, and aflatoxin exposure. Current treatments for advanced HCC are limited, necessitating new therapies. γδT cells, a unique T-cell subset, exhibit strong antitumor activity in pre-clinical studies, making them promising for adoptive cell therapy.

Objective: This study aims to explore the role of γδT cells in the HCC microenvironment and to evaluate the antitumor efficacy of CAR-engineered γδT (CAR-γδT) cells as a novel immunotherapy. Specifically, it investigates the relationship between γδT-cell infiltration and overall survival in HCC patients.

Methods: Using the Cancer Genome Atlas data, patients were stratified into high- and low-infiltration groups based on γδT-cell gene signatures. Survival analysis and immune cell profiling were performed. Multicolor immunofluorescence was conducted on HCC tissues from 12 short-survival (<5 years) and 15 long-survival (5 years) patients to analyze γδT-cell distribution.

Results: The high-infiltration group had significantly longer overall survival (p<0.05). This group also showed higher proportions of CD8+ T cells and M1 macrophages, but lower M2 macrophages (p<0.05). In long-survival patients, γδT cells mainly infiltrated the tumor core, whereas in short-survival patients, they accumulated at the tumor margin. CD8+ T-cell abundance correlated strongly with γδT cells, and better prognosis was associated with higher natural killer group 2 member D ligand expression.

Conclusion: High γδT-cell infiltration in HCC correlates with improved prognosis, highlighting γδT cells as a potential antitumor effector subset and a promising prognostic marker.

Keywords
γδT cell
Hepatocellular carcinoma
Prognosis
Immune microenvironment
Funding
This study was supported by The First Affiliated Hospital, Shihezi University, under the project titled “Basic Research on γδ T Cell-based Chimeric Antigen Receptor T-Cell Therapy for Liver Cancer” (BS202203).
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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