Lu Xinjun, Green Benjamin L, Xie Changqing, Liu Chao, Chen Xin
Department of Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Cancer Biology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
JHEP Rep. 2023 Mar 9;5(7):100723. doi: 10.1016/j.jhepr.2023.100723. eCollection 2023 Jul.
Cholangiocarcinoma (CCA) is a rare primary liver cancer associated with high mortality and few systemic treatment options. The behaviour of the immune system has come into focus as a potential treatment modality for many cancer types, but immunotherapy has yet to dramatically alter the treatment paradigm for CCA as it has for other diseases. Herein, we review recent studies describing the relevance of the tumour immune microenvironment (TIME) in CCA. Various non-parenchymal cell types are critically important in controlling CCA progression, prognosis, and response to systemic therapy. Knowledge of the behaviour of these leukocytes could help generate hypotheses to guide the development of potential immune-directed therapies. Recently, an immunotherapy-containing combination was approved for the treatment of advanced-stage CCA. However, despite level 1 evidence demonstrating the improved efficacy of this therapy, survival remained suboptimal. In the current manuscript, we provide a comprehensive review of the TIME in CCA, preclinical studies of immunotherapies against CCA, as well as ongoing clinical trials applying immunotherapies for the treatment of CCA. Particular emphasis is placed on microsatellite unstable tumours, a rare CCA subtype that demonstrates heightened sensitivity to approved immune checkpoint inhibitors. We also discuss the challenges involved in applying immunotherapies to the treatment of CCA and the importance of understanding the TIME.
胆管癌（CCA）是一种罕见的原发性肝癌，死亡率高且全身治疗选择有限。免疫系统的作用已成为许多癌症类型的一种潜在治疗方式，但免疫疗法尚未像对其他疾病那样显著改变CCA的治疗模式。在此，我们综述了近期描述肿瘤免疫微环境（TIME）在CCA中的相关性的研究。各种非实质细胞类型在控制CCA进展、预后及对全身治疗的反应方面至关重要。了解这些白细胞的行为有助于提出假设，以指导潜在免疫导向疗法的开发。最近，一种含免疫疗法的联合方案被批准用于治疗晚期CCA。然而，尽管有一级证据表明该疗法疗效有所提高，但生存率仍不理想。在本手稿中，我们全面综述了CCA中的TIME、针对CCA的免疫疗法的临床前研究以及正在进行的应用免疫疗法治疗CCA的临床试验。特别强调微卫星不稳定肿瘤，这是一种罕见的CCA亚型，对已批准的免疫检查点抑制剂表现出更高的敏感性。我们还讨论了将免疫疗法应用于CCA治疗所涉及的挑战以及了解TIME的重要性。
