Natural killer cell therapy in hepatocellular carcinoma: a comprehensive review

Abstract Hepatocellular carcinoma remains a major healthcare burden worldwide and is predicted to be the cause of death of 1.3 million people in 2040. Most HCC patients are diagnosed in advanced stages, leading to a poor prognosis. The development of targeted immunotherapies is essential to address...

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Main Authors: Shirin Tavakoli, Maryam Samareh-Salavati, Mahshid Akhavan Rahnama, Shahrokh Abdolahi, Ali Hassanzadeh, Zeinab Ghazvinian, Javad Verdi, Nasim Vousooghi, Saba Manoochehrabadi, Bahram Chahardouli, Maryam Barkhordar, Iman Seyhoun, Mohammad Ahmadvand
Format: Article
Language:English
Published: Springer 2025-07-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-03138-2
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author Shirin Tavakoli
Maryam Samareh-Salavati
Mahshid Akhavan Rahnama
Shahrokh Abdolahi
Ali Hassanzadeh
Zeinab Ghazvinian
Javad Verdi
Nasim Vousooghi
Saba Manoochehrabadi
Bahram Chahardouli
Maryam Barkhordar
Iman Seyhoun
Mohammad Ahmadvand
author_facet Shirin Tavakoli
Maryam Samareh-Salavati
Mahshid Akhavan Rahnama
Shahrokh Abdolahi
Ali Hassanzadeh
Zeinab Ghazvinian
Javad Verdi
Nasim Vousooghi
Saba Manoochehrabadi
Bahram Chahardouli
Maryam Barkhordar
Iman Seyhoun
Mohammad Ahmadvand
author_sort Shirin Tavakoli
collection DOAJ
description Abstract Hepatocellular carcinoma remains a major healthcare burden worldwide and is predicted to be the cause of death of 1.3 million people in 2040. Most HCC patients are diagnosed in advanced stages, leading to a poor prognosis. The development of targeted immunotherapies is essential to address this unmet clinical challenge. Natural killer (NK) cells have emerged as a promising cell-based therapeutic approach for treating solid tumors. NK cells have the distinctive ability to identify and destroy cancer cells without requiring prior sensitization. Here, we discuss potential approaches, developing strategies, and current challenges of NK cell therapy reported completely. In addition, advancements in immunotherapy, including adoptive NK cell therapy, and the strategies to boost NK cell function against HCC such as cytokine-based treatments, immune checkpoint inhibitors, vaccine-based approaches, genetic delivery, non-coding RNAs, antibody-based methods, and natural agents have been discussed. This comprehensive study provides a unique perspective by integrating recent findings on the differential impact of NK cells on HCC. We highlight the latest advances in NK cell engineering and immune checkpoint modulation, presenting a comparative analysis of therapeutic strategies. Furthermore, we critically assess the translational challenges associated with NK cell-based therapies, particularly focusing on their limited in vivo persistence and tumor immune evasion strategies.
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institution Kabale University
issn 2730-6011
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publishDate 2025-07-01
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series Discover Oncology
spelling doaj-art-be567ee2183c4c1795e64687ae2cb3592025-08-20T03:43:03ZengSpringerDiscover Oncology2730-60112025-07-0116112110.1007/s12672-025-03138-2Natural killer cell therapy in hepatocellular carcinoma: a comprehensive reviewShirin Tavakoli0Maryam Samareh-Salavati1Mahshid Akhavan Rahnama2Shahrokh Abdolahi3Ali Hassanzadeh4Zeinab Ghazvinian5Javad Verdi6Nasim Vousooghi7Saba Manoochehrabadi8Bahram Chahardouli9Maryam Barkhordar10Iman Seyhoun11Mohammad Ahmadvand12Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesDepartment of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesCell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical SciencesBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesDepartment of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesBasic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical SciencesDepartment of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesDepartment of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesPediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical SciencesCell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical SciencesCell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical SciencesDepartment of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesCell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical SciencesAbstract Hepatocellular carcinoma remains a major healthcare burden worldwide and is predicted to be the cause of death of 1.3 million people in 2040. Most HCC patients are diagnosed in advanced stages, leading to a poor prognosis. The development of targeted immunotherapies is essential to address this unmet clinical challenge. Natural killer (NK) cells have emerged as a promising cell-based therapeutic approach for treating solid tumors. NK cells have the distinctive ability to identify and destroy cancer cells without requiring prior sensitization. Here, we discuss potential approaches, developing strategies, and current challenges of NK cell therapy reported completely. In addition, advancements in immunotherapy, including adoptive NK cell therapy, and the strategies to boost NK cell function against HCC such as cytokine-based treatments, immune checkpoint inhibitors, vaccine-based approaches, genetic delivery, non-coding RNAs, antibody-based methods, and natural agents have been discussed. This comprehensive study provides a unique perspective by integrating recent findings on the differential impact of NK cells on HCC. We highlight the latest advances in NK cell engineering and immune checkpoint modulation, presenting a comparative analysis of therapeutic strategies. Furthermore, we critically assess the translational challenges associated with NK cell-based therapies, particularly focusing on their limited in vivo persistence and tumor immune evasion strategies.https://doi.org/10.1007/s12672-025-03138-2Hepatocellular carcinomaNatural killer cellsImmunotherapySolid tumorsCancer therapy
spellingShingle Shirin Tavakoli
Maryam Samareh-Salavati
Mahshid Akhavan Rahnama
Shahrokh Abdolahi
Ali Hassanzadeh
Zeinab Ghazvinian
Javad Verdi
Nasim Vousooghi
Saba Manoochehrabadi
Bahram Chahardouli
Maryam Barkhordar
Iman Seyhoun
Mohammad Ahmadvand
Natural killer cell therapy in hepatocellular carcinoma: a comprehensive review
Discover Oncology
Hepatocellular carcinoma
Natural killer cells
Immunotherapy
Solid tumors
Cancer therapy
title Natural killer cell therapy in hepatocellular carcinoma: a comprehensive review
title_full Natural killer cell therapy in hepatocellular carcinoma: a comprehensive review
title_fullStr Natural killer cell therapy in hepatocellular carcinoma: a comprehensive review
title_full_unstemmed Natural killer cell therapy in hepatocellular carcinoma: a comprehensive review
title_short Natural killer cell therapy in hepatocellular carcinoma: a comprehensive review
title_sort natural killer cell therapy in hepatocellular carcinoma a comprehensive review
topic Hepatocellular carcinoma
Natural killer cells
Immunotherapy
Solid tumors
Cancer therapy
url https://doi.org/10.1007/s12672-025-03138-2
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