Gehl Virag, O'Rourke Colm J, Andersen Jesper B
Department of Health and Medical Sciences, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
Hepatology. 2023 Nov 16. doi: 10.1097/HEP.0000000000000688.
The development of cholangiocarcinoma spans years, if not decades, during which the immune system becomes corrupted and permissive to primary tumor development and metastasis. This involves subversion of local immunity at tumor sites, as well as systemic immunity and the wider host response. While immune dysfunction is a hallmark of all cholangiocarcinoma, the specific steps of the cancer-immunity cycle that are perturbed differ between patients. Heterogeneous immune functionality impacts the evolutionary development, pathobiological behavior, and therapeutic response of these tumors. Integrative genomic analyses of thousands of primary tumors have supported a biological rationale for immune-based stratification of patients, encompassing immune cell composition and functionality. However, discerning immune alterations responsible for promoting tumor initiation, maintenance, and progression from those present as bystander events remains challenging. Functionally uncoupling the tumor-promoting or tumor-suppressing roles of immune profiles will be critical for identifying new immunomodulatory treatment strategies and associated biomarkers for patient stratification. This review will discuss the immunogenomics of cholangiocarcinoma, including the impact of genomic alterations on immune functionality, subversion of the cancer-immunity cycle, as well as clinical implications for existing and novel treatment strategies.
胆管癌的发展历经数年，甚至数十年，在此期间免疫系统遭到破坏，使得原发性肿瘤得以发展并发生转移。这涉及肿瘤部位局部免疫、全身免疫以及更广泛的宿主反应的颠覆。虽然免疫功能障碍是所有胆管癌的一个标志，但不同患者的癌症免疫循环中受到干扰的具体步骤有所不同。免疫功能的异质性会影响这些肿瘤的进化发展、病理生物学行为及治疗反应。对数千个原发性肿瘤进行的综合基因组分析为基于免疫的患者分层提供了生物学依据，包括免疫细胞组成和功能。然而，区分那些促进肿瘤起始、维持和进展的免疫改变与作为旁观者事件出现的免疫改变仍然具有挑战性。从功能上区分免疫特征的促肿瘤或抑肿瘤作用对于确定新的免疫调节治疗策略以及用于患者分层的相关生物标志物至关重要。本综述将讨论胆管癌的免疫基因组学，包括基因组改变对免疫功能的影响、癌症免疫循环的颠覆，以及对现有和新型治疗策略的临床意义。
