Giraud Julie, Chalopin Domitille, Blanc Jean-Frédéric, Saleh Maya
University of Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, Bordeaux, France.
University of Bordeaux, INSERM UMR 1053, Bordeaux, France.
Front Immunol. 2021 Mar 18;12:655697. doi: 10.3389/fimmu.2021.655697. eCollection 2021.
Hepatocellular carcinoma (HCC) is the most common liver tumor and among the deadliest cancers worldwide. Advanced HCC overall survival is meager and has not improved over the last decade despite approval of several tyrosine kinase inhibitors (TKi) for first and second-line treatments. The recent approval of immune checkpoint inhibitors (ICI) has revolutionized HCC palliative care. Unfortunately, the majority of HCC patients fail to respond to these therapies. Here, we elaborate on the immune landscapes of the normal and cirrhotic livers and of the unique HCC tumor microenvironment. We describe the molecular and immunological classifications of HCC, discuss the role of specific immune cell subsets in this cancer, with a focus on myeloid cells and pathways in anti-tumor immunity, tumor promotion and immune evasion. We also describe the challenges and opportunities of immunotherapies in HCC and discuss new avenues based on harnessing the anti-tumor activity of myeloid, NK and γδ T cells, vaccines, chimeric antigen receptors (CAR)-T or -NK cells, oncolytic viruses, and combination therapies.
肝细胞癌（HCC）是最常见的肝脏肿瘤，也是全球最致命的癌症之一。晚期HCC的总体生存率很低，尽管过去十年间已有多种酪氨酸激酶抑制剂（TKi）获批用于一线和二线治疗，但生存率并未得到改善。免疫检查点抑制剂（ICI）最近获批，彻底改变了HCC的姑息治疗。不幸的是，大多数HCC患者对这些疗法没有反应。在此，我们详细阐述正常肝脏、肝硬化肝脏以及独特的HCC肿瘤微环境的免疫格局。我们描述了HCC的分子和免疫分类，讨论了特定免疫细胞亚群在这种癌症中的作用，重点关注髓系细胞以及抗肿瘤免疫、肿瘤促进和免疫逃逸中的相关途径。我们还描述了HCC免疫治疗的挑战和机遇，并讨论基于利用髓系细胞、自然杀伤细胞（NK）和γδT细胞的抗肿瘤活性、疫苗、嵌合抗原受体（CAR）-T或-NK细胞、溶瘤病毒以及联合疗法的新途径。
