The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu Province 210009, China.
Hepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Transplantation, Chinese Academy of Medical Sciences, Nanjing, Jiangsu Province 210029, China; Department of General Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Cell Signal. 2024 Dec;124:111405. doi: 10.1016/j.cellsig.2024.111405. Epub 2024 Sep 12.
Hepatocellular carcinoma (HCC), a major subtype of liver cancer, poses significant therapeutic challenges due to its late diagnosis and rapid progression. The evolving landscape of immunotherapy offers a beacon of hope, with natural killer (NK) cells emerging as pivotal players in combating HCC. NK cells are unique cytotoxic lymphocytes that are essential in the fight against infections and malignancies. Phenotypic and functional NK cell abnormalities have been shown in HCC patients, indicating their significance as a component of the innate immune system against cancer. This review elucidates the critical role of NK cells in combating HCC, focusing on their interaction with the tumor microenvironment, the development of NK cell-based therapies, and the innovative strategies to enhance their efficacy in the immunosuppressive milieu of HCC. The review delves into the various therapeutic strategies, including autologous and allogeneic NK cell therapies, genetic engineering to improve NK cell resilience and targeting, and the integration of NK cells with other immunotherapeutic approaches like checkpoint inhibitors and oncolytic virotherapy. By highlighting recent advancements and the ongoing challenges in the field, this review sets the stage for future research directions that could unlock the full potential of NK cell-based immunotherapy for HCC, offering a beacon of hope for patients battling this formidable cancer.
肝细胞癌（HCC）是肝癌的主要亚型，由于其诊断较晚且进展迅速，因此治疗极具挑战性。免疫疗法的不断发展为我们带来了一线希望，自然杀伤（NK）细胞作为抗击 HCC 的关键因素崭露头角。NK 细胞是独特的细胞毒性淋巴细胞，在抗感染和恶性肿瘤中发挥着重要作用。在 HCC 患者中已经观察到表型和功能 NK 细胞异常，表明它们作为固有免疫系统对抗癌症的一个组成部分具有重要意义。本综述阐明了 NK 细胞在抗击 HCC 中的关键作用，重点介绍了它们与肿瘤微环境的相互作用、基于 NK 细胞的治疗方法的发展，以及在 HCC 的免疫抑制环境中增强其疗效的创新策略。本综述深入探讨了各种治疗策略，包括自体和同种异体 NK 细胞治疗、提高 NK 细胞抵抗力和靶向性的基因工程，以及将 NK 细胞与其他免疫治疗方法（如检查点抑制剂和溶瘤病毒治疗）相结合。通过强调该领域的最新进展和当前挑战，本综述为未来的研究方向奠定了基础，这些研究方向可能为基于 NK 细胞的免疫疗法治疗 HCC 释放出全部潜力，为抗击这种可怕癌症的患者带来希望。
