School of Medicine, Division of Gastroenterology and Hepatology, Marmara University, Istanbul, Turkey.
J Gastrointest Cancer. 2021 Dec;52(4):1217-1222. doi: 10.1007/s12029-021-00758-z. Epub 2021 Dec 11.
In recent years, immune-based therapies have emerged as novel pillars for hepatocellular carcinoma (HCC). The rationale of immune-checkpoint inhibitors (ICIs) trial in HCC originated from the fact that the tumor cells and the infiltrating stromal and immune cells promote an immunosuppressive tumor microenvironment, including the up-regulation of immune checkpoint molecules on their surface. Antibody-based blockage targeting inhibitory checkpoint molecules on cytotoxic T cells, including programmed cell death-1 (PD-1) or its counterpart on antigen-presenting cells has shown strong anti-tumor activity in a subset of HCC patients. Single nucleotide polymorphisms (SNP) of PD-1 gene may affect the PD-1 expression or function, which eventually can cause dysfunctionality of immune balance. Based on the inhibitory role of PD-1 in anti-tumor responses, it has been investigated in several studies as a candidate to test for genetic susceptibility of individuals to HCC. The present paper highlights the knowledge on cross-talks for liver immunology and HCC course, recent studies investigating the role of functional SNPs of PD-1 gene in Turkish HCC population, and the data on already investigated PD-1 inhibitor molecules in clinical trials.
近年来，免疫疗法已成为肝细胞癌 (HCC) 的新支柱。 HCC 中免疫检查点抑制剂 (ICI) 试验的原理源于肿瘤细胞和浸润的基质及免疫细胞促进免疫抑制性肿瘤微环境这一事实，包括其表面免疫检查点分子的上调。针对细胞毒性 T 细胞上抑制性检查点分子的基于抗体的阻断，包括程序性细胞死亡蛋白-1 (PD-1) 或其在抗原呈递细胞上的对应物，在一部分 HCC 患者中显示出很强的抗肿瘤活性。PD-1 基因的单核苷酸多态性 (SNP) 可能影响 PD-1 的表达或功能，最终导致免疫平衡的功能障碍。基于 PD-1 在抗肿瘤反应中的抑制作用，它已在几项研究中被作为个体对 HCC 遗传易感性的候选基因进行了研究。本文重点介绍了肝脏免疫学和 HCC 病程的相互作用知识、最近研究中 PD-1 基因功能 SNP 在土耳其 HCC 人群中的作用，以及临床试验中已研究的 PD-1 抑制剂分子的数据。
