Minaei Neda, Ramezankhani Roya, Tamimi Atena, Piryaei Abbas, Zarrabi Ali, Aref Amir Reza, Mostafavi Ebrahim, Vosough Massoud
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran.
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran; Department of Development and Regeneration, KU Leuven Stem Cell Institute, Leuven, Belgium.
Eur J Cell Biol. 2023 Mar;102(1):151284. doi: 10.1016/j.ejcb.2022.151284. Epub 2022 Dec 17.
Hepatocellular carcinoma (HCC) is the most common type of primary hepatic cancer and is among the major causes of mortality due to cancer. Due to the lack of efficient conventional therapeutic options for this cancer, particularly in advanced cases, novel treatments including immunotherapy have been considered. However, despite the encouraging clinical outcomes after implementing these innovative approaches, such as oncolytic viruses (OVs), adoptive cell therapies (ACT), immune checkpoint blockades (ICBs), and cancer vaccines, several factors have restricted their therapeutic effect. The main concern is the existence of an immunosuppressive tumor microenvironment (TME). Combination of different ICBs or ICBs plus tyrosine kinase inhibitors have shown promising results in overcoming these limiting factors to some extent. Combination of programmed cell death ligand-1 (PD-L1) antibody Atezolizumab and vascular endothelial growth factor (VEGF) antibody Bevacizumab has become the standard of care in the first-line therapy for untestable HCC, approved by regulatory agencies. This paper highlighted a wide overview of the direct and indirect immunotherapeutic strategies proposed for the treatment of HCC patients and the common challenges that have hindered their further clinical applications.
肝细胞癌(HCC)是原发性肝癌最常见的类型,也是癌症致死的主要原因之一。由于针对这种癌症缺乏有效的传统治疗选择,尤其是在晚期病例中,包括免疫疗法在内的新疗法已被纳入考虑范围。然而,尽管实施这些创新方法(如溶瘤病毒(OVs)、过继性细胞疗法(ACT)、免疫检查点阻断(ICB)和癌症疫苗)后取得了令人鼓舞的临床结果,但仍有几个因素限制了它们的治疗效果。主要问题在于免疫抑制性肿瘤微环境(TME)的存在。不同ICB的联合使用或ICB加酪氨酸激酶抑制剂在一定程度上克服这些限制因素方面已显示出有前景的结果。程序性细胞死亡配体1(PD-L1)抗体阿替利珠单抗和血管内皮生长因子(VEGF)抗体贝伐单抗的联合使用已成为不可检测的HCC一线治疗的标准治疗方案,并已获得监管机构的批准。本文重点概述了为治疗HCC患者而提出的直接和间接免疫治疗策略,以及阻碍它们进一步临床应用的常见挑战。
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