华文简明版如下： 肝内胆管细胞癌（ICC）是一种预后差的高度侵袭性肝肿瘤。近来，免疫检查点抑制剂（ICIs），如程序性细胞死亡1（PD-1）抑制剂，已经成为多种肿瘤类型的一种有前景的治疗策略，包括ICC。微卫星不稳定高（MSI-H）是固体肿瘤ICIs的一个重要生物标志物。MSI-H患者的响应率明显高于微卫星稳定性/微卫星不稳定低的患者。大约80-90％的MSI-H患者在初始治疗获得初步反应后能够持续获得临床益处。然而，一些患者可能在初始阶段就表现出原发性耐药性，而在长期治疗后某些患者可能会获得后期耐药性。我们报告了一个ICIs在这种MSI-H案例中快速获得耐药性的ICC患者的病例，该患者在卡姆瑞利珠单抗（一种PD-1抑制剂）作为二线治疗的短期缓解后迅速进展。通过下一代测序和多重免疫荧光染色对该患者的基因组和免疫特征进行了分析，以探索该MSI-H病例的ICIs迅速获得耐药性的可能机制。基因组和免疫组化分析显示，该MSI-H患者ICIs的不持续效益可能与TGFBR2突变、HLA B44超型缺失、携带B62超型以及肿瘤微环境中PD-L1+细胞、巨噬细胞和Treg的增加有关。 © 2023 作者. 由 S. Karger AG, Basel发表。

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive liver malignancy with poor prognosis. Recently, the development of immune checkpoint inhibitors (ICIs), such as programmed cell death 1 (PD-1) inhibitors, has emerged as a promising strategy in multiple tumor types, including ICC. Microsatellite instability-high (MSI-H) is an important biomarker for ICIs in solid tumors. The response rate in patients with MSI-H is significantly higher than in those with microsatellite stability/microsatellite instability-low. And approximately 80-90% of the patients with MSI-H could maintain sustained clinical benefits once they had an initial response. However, some patients could have primary resistance at the beginning, and some might have acquired resistance after long-term treatment.We present the case of an ICC patient with MSI-H who suffered rapid progression after a short-term remission with camrelizumab, a kind of PD-1 inhibitor, as second-line treatment. The patient's genomic and immune features were analyzed by next-generation sequencing and multiplex immunofluorescence staining to explore the possible mechanisms of the rapidly acquired resistance of ICIs in this MSI-H case.The genomic and immunohistochemical analysis showed that TGFBR2 mutation, loss of HLA B44 supertype, carrying B62 supertype, and increased PD-L1+ cells, macrophages, and Tregs in the tumor microenvironment might be related to the nonsustain benefit of ICIs in this MSI-H patient.© 2023 The Author(s). Published by S. Karger AG, Basel.