Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Expert Opin Investig Drugs. 2021 Apr;30(4):429-438. doi: 10.1080/13543784.2021.1865308. Epub 2020 Dec 28.
Cholangiocarcinomas (CCAs) are biliary epithelial tumors with rising incidence over the past 3 decades. Early diagnosis of CCAs remains a significant challenge and the majority of patients present at an advanced stage. CCAs are heterogeneous tumors and currently available standard systemic therapy options are of limited effectiveness. Immune checkpoint inhibition (ICI) has transformed cancer therapy across a spectrum of malignancies. However, the response rate to ICI has been relatively disappointing in CCAs owing to its desmoplastic tumor microenvironment (TME).: Tumor microenvironment of CCAs consists of innate and adaptive cells, stromal cells, and extracellular components (cytokines, chemokines, exosomes, etc.). This intricate microenvironment has multiple immunosuppressive elements that promote tumor cell survival and therapeutic resistance. Accordingly, there is a need for the development of effective therapeutic strategies that target the TME. Herein, we review the components of the CCA TME, and potential therapies targeting the CCA TME.: CCAs are desmoplastic tumors with a dense tumor microenvironment. An enhanced understanding of the various components of the CCA TME is essential in the effort to develop novel biomarkers for patient stratification as well as combination therapeutic strategies that target the tumor plus the TME.
胆管癌（CCA）是一种胆道上皮肿瘤，在过去 30 年中发病率不断上升。CCA 的早期诊断仍然是一个重大挑战，大多数患者就诊时已处于晚期。CCA 是异质性肿瘤，目前可用的标准系统治疗方案效果有限。免疫检查点抑制（ICI）已经改变了多种恶性肿瘤的治疗方法。然而，由于其纤维母细胞瘤微环境（TME），ICI 在 CCA 中的反应率相对令人失望：CCA 的肿瘤微环境由先天和适应性细胞、基质细胞和细胞外成分（细胞因子、趋化因子、外泌体等）组成。这种复杂的微环境有多个免疫抑制因素，促进肿瘤细胞的存活和治疗抵抗。因此，需要开发针对 TME 的有效治疗策略。本文综述了 CCA TME 的组成部分，以及针对 CCA TME 的潜在治疗方法：CCA 是一种纤维母细胞瘤，其肿瘤微环境致密。深入了解 CCA TME 的各种成分对于开发新的生物标志物以进行患者分层以及针对肿瘤和 TME 的联合治疗策略至关重要。
