Genomic and Immune Features in an Intrahepatic Cholangiocarcinoma Patient with Microsatellite Instability-High Suffered Rapid Acquired Resistance to PD-1 Inhibitor

Introduction: 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. Case Presentation: 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. Conclusion: 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.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Genomic and Immune Features in an Intrahepatic Cholangiocarcinoma Patient with Microsatellite Instability-High Suffered Rapid Acquired Resistance to PD-1 Inhibitor ; volume:12 ; number:3 ; year:2023 ; pages:281-288 ; extent:8
Liver cancer ; 12, Heft 3 (2023), 281-288 (gesamt 8)

Creator
Cheng, Zhuo
Zeng, Tianmei
Yang, Guang
Liu, Di
Zheng, Zhi
Yuan, Zhengang

DOI
10.1159/000530273
URN
urn:nbn:de:101:1-2023081700304354191282
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:57 AM CEST

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Associated

  • Cheng, Zhuo
  • Zeng, Tianmei
  • Yang, Guang
  • Liu, Di
  • Zheng, Zhi
  • Yuan, Zhengang

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