Application and prospect analysis of chimeric antigen receptor T-cell therapy in hepatocellular carcinoma treatment: a systematic review and meta-analysis

IntroductionHepatocellular carcinoma (HCC), accounting for 90% of primary liver cancers, is a high-mortality malignancy and the third leading cause of cancer-related deaths globally, with major risk factors like hepatitis B/C, aflatoxin exposure, and obesity. Most patients are diagnosed at advanced...

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Main Authors: Sichang Wu, Xinli Gan, Shuxin Huang, Yujun Zhong, Jialin Wu, Haojie Yang, Bangde Xiang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1566976/full
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author Sichang Wu
Sichang Wu
Xinli Gan
Shuxin Huang
Yujun Zhong
Jialin Wu
Haojie Yang
Haojie Yang
Bangde Xiang
author_facet Sichang Wu
Sichang Wu
Xinli Gan
Shuxin Huang
Yujun Zhong
Jialin Wu
Haojie Yang
Haojie Yang
Bangde Xiang
author_sort Sichang Wu
collection DOAJ
description IntroductionHepatocellular carcinoma (HCC), accounting for 90% of primary liver cancers, is a high-mortality malignancy and the third leading cause of cancer-related deaths globally, with major risk factors like hepatitis B/C, aflatoxin exposure, and obesity. Most patients are diagnosed at advanced stages, with a 5-year survival rate below 10%. Therefore, HCC treatment and research still face significant challenges, and more effective treatments need to be further explored.MethodsWe searched PubMed, Scopus, Web of Science and Embase from the time of repository construction to March 1, 2025, preliminary included studies involving animal experiments on the therapeutic effects of Chimeric Antigen Receptor T-cell (CAR-T cell) therapy on HCC. After exclusion and evaluation of literature, the random/fixed effects model was employed to perform meta-analysis and obtain Weighted Mean Difference (WMD) and 95% confidence interval (CI) of tumor volume and mass. We then verify the robustness of the results through subgroup analysis and sensitivity analysis. Use Q-test to evaluate heterogeneity and quantify it based on I² value.ResultsWe included a total of 16 studies. Multiple independent sets of data were extracted from the experiments of these studies, of which 25 were used for volume-based meta-analysis and 16 were used for mass-based meta-analysis. Regarding volume, The combined mean CAR-T treatment group/control group resulted in an WMD of -515.77 (95% CI: -634.78 to -396.76; I² =90.8%). Meanwhile, based on mass, the combined mean CAR-T treatment group/control group resulted in an WMD of -0.30 (95% CI: -0.38 to -0.22; I² = 94.4%). The results of the bias analysis further validated the reliability of the research conclusions.ConclusionsBased on the dual-index meta-analysis, the CAR-T therapy have been proved to possess significant therapeutic effect in HCC. However, the funnel plot of tumor mass and the Egger’s regression suggest the potential presence of publication bias. Thus, it warrants further research to evaluate the potential of CAR-T therapy alone or as an adjuvant for HCC treatment.
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issn 1664-3224
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publishDate 2025-04-01
publisher Frontiers Media S.A.
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series Frontiers in Immunology
spelling doaj-art-de66fb3d53334630933360cf17e99f912025-08-20T03:17:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15669761566976Application and prospect analysis of chimeric antigen receptor T-cell therapy in hepatocellular carcinoma treatment: a systematic review and meta-analysisSichang Wu0Sichang Wu1Xinli Gan2Shuxin Huang3Yujun Zhong4Jialin Wu5Haojie Yang6Haojie Yang7Bangde Xiang8Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, ChinaThe Second Clinical Medical College of Guangxi Medical University, Nanning, ChinaThe Second Clinical Medical College of Guangxi Medical University, Nanning, ChinaThe Second Clinical Medical College of Guangxi Medical University, Nanning, ChinaThe Second Clinical Medical College of Guangxi Medical University, Nanning, ChinaThe Second Clinical Medical College of Guangxi Medical University, Nanning, ChinaDepartment of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, ChinaDepartment of Hepatobiliary Surgery, Changde Hospital (The First People’s Hospital of Changde), Xiangya School of Medicine, Central South University, Changde, ChinaDepartment of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, ChinaIntroductionHepatocellular carcinoma (HCC), accounting for 90% of primary liver cancers, is a high-mortality malignancy and the third leading cause of cancer-related deaths globally, with major risk factors like hepatitis B/C, aflatoxin exposure, and obesity. Most patients are diagnosed at advanced stages, with a 5-year survival rate below 10%. Therefore, HCC treatment and research still face significant challenges, and more effective treatments need to be further explored.MethodsWe searched PubMed, Scopus, Web of Science and Embase from the time of repository construction to March 1, 2025, preliminary included studies involving animal experiments on the therapeutic effects of Chimeric Antigen Receptor T-cell (CAR-T cell) therapy on HCC. After exclusion and evaluation of literature, the random/fixed effects model was employed to perform meta-analysis and obtain Weighted Mean Difference (WMD) and 95% confidence interval (CI) of tumor volume and mass. We then verify the robustness of the results through subgroup analysis and sensitivity analysis. Use Q-test to evaluate heterogeneity and quantify it based on I² value.ResultsWe included a total of 16 studies. Multiple independent sets of data were extracted from the experiments of these studies, of which 25 were used for volume-based meta-analysis and 16 were used for mass-based meta-analysis. Regarding volume, The combined mean CAR-T treatment group/control group resulted in an WMD of -515.77 (95% CI: -634.78 to -396.76; I² =90.8%). Meanwhile, based on mass, the combined mean CAR-T treatment group/control group resulted in an WMD of -0.30 (95% CI: -0.38 to -0.22; I² = 94.4%). The results of the bias analysis further validated the reliability of the research conclusions.ConclusionsBased on the dual-index meta-analysis, the CAR-T therapy have been proved to possess significant therapeutic effect in HCC. However, the funnel plot of tumor mass and the Egger’s regression suggest the potential presence of publication bias. Thus, it warrants further research to evaluate the potential of CAR-T therapy alone or as an adjuvant for HCC treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1566976/fullCAR-T therapyhepatocellular carcinomaimmunotherapymeta-analysissystematic review
spellingShingle Sichang Wu
Sichang Wu
Xinli Gan
Shuxin Huang
Yujun Zhong
Jialin Wu
Haojie Yang
Haojie Yang
Bangde Xiang
Application and prospect analysis of chimeric antigen receptor T-cell therapy in hepatocellular carcinoma treatment: a systematic review and meta-analysis
Frontiers in Immunology
CAR-T therapy
hepatocellular carcinoma
immunotherapy
meta-analysis
systematic review
title Application and prospect analysis of chimeric antigen receptor T-cell therapy in hepatocellular carcinoma treatment: a systematic review and meta-analysis
title_full Application and prospect analysis of chimeric antigen receptor T-cell therapy in hepatocellular carcinoma treatment: a systematic review and meta-analysis
title_fullStr Application and prospect analysis of chimeric antigen receptor T-cell therapy in hepatocellular carcinoma treatment: a systematic review and meta-analysis
title_full_unstemmed Application and prospect analysis of chimeric antigen receptor T-cell therapy in hepatocellular carcinoma treatment: a systematic review and meta-analysis
title_short Application and prospect analysis of chimeric antigen receptor T-cell therapy in hepatocellular carcinoma treatment: a systematic review and meta-analysis
title_sort application and prospect analysis of chimeric antigen receptor t cell therapy in hepatocellular carcinoma treatment a systematic review and meta analysis
topic CAR-T therapy
hepatocellular carcinoma
immunotherapy
meta-analysis
systematic review
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1566976/full
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