Tavakoli Shirin, Samareh-Salavati Maryam, Rahnama Mahshid Akhavan, Abdolahi Shahrokh, Hassanzadeh Ali, Ghazvinian Zeinab, Verdi Javad, Vousooghi Nasim, Manoochehrabadi Saba, Chahardouli Bahram, Barkhordar Maryam, Seyhoun Iman, Ahmadvand Mohammad
Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran.
Discov Oncol. 2025 Jul 16;16(1):1348. doi: 10.1007/s12672-025-03138-2.
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.
肝细胞癌仍然是全球主要的医疗负担，预计到2040年将导致130万人死亡。大多数肝癌患者在晚期被诊断出来，预后较差。开发靶向免疫疗法对于应对这一未满足的临床挑战至关重要。自然杀伤（NK）细胞已成为一种有前途的基于细胞的实体瘤治疗方法。NK细胞具有独特的能力，无需预先致敏就能识别并摧毁癌细胞。在此，我们全面讨论了NK细胞疗法的潜在方法、开发策略和当前挑战。此外，还讨论了免疫疗法的进展，包括过继性NK细胞疗法，以及增强NK细胞抗肝癌功能的策略，如基于细胞因子的治疗、免疫检查点抑制剂、基于疫苗的方法、基因递送、非编码RNA、基于抗体的方法和天然药物。这项综合性研究通过整合近期关于NK细胞对肝癌不同影响的研究结果，提供了一个独特的视角。我们强调了NK细胞工程和免疫检查点调节方面的最新进展，对治疗策略进行了比较分析。此外，我们批判性地评估了与基于NK细胞的疗法相关的转化挑战，尤其关注其在体内有限的持久性和肿瘤免疫逃逸策略。
