ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025
Multiple-omics analysis reveals a dedifferentiation-immune loop in intrahepatic cholangiocarcinoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Role of the stromal and immune microenvironment in intrahepatic cholangiocarcinoma.JHEP reports : innovation in hepatology · 2026Review
- Spatial immune atlas of breast cancer brain metastasis reveals CD163Journal for immunotherapy of cancer · 2026Article
- Single-cell multi-omics in biliary tract cancers: decoding heterogeneity, microenvironment, and treatment strategies.Molecular biomedicine · 2025Review
- Review: Progress of the NLRP3 inflammasome in tumours and perspectives for cholangiocarcinoma.Cell communication and signaling : CCS · 2025Review
- Precision medicine for advanced biliary tract cancer in China: current status and future perspectives.Frontiers of medicine · 2025Review
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Authors and funding
18 authors.
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Abstract
Intrahepatic cholangiocarcinoma (ICC) is known for its diverse cell types and resistance to standard treatments, highlighting the importance of understanding its tumor microenvironment (TME) for improved prognostic accuracy and therapeutic innovation. Our study used a multi-omics approach to analyze the ICC TME in both human and mouse samples, linking survival outcomes to the complex cellular interactions within the TME. We discovered a dedifferentiation phenomenon in ICC cells driven by the Yes-associated protein (YAP) pathway, influenced by tumor-associated macrophages (TAMs). Conversely, ICC cells promoted an immunosuppressive environment in TAMs. Targeting TAMs in a transgenic mouse model disrupted this loop, enhancing T cell responses and suggesting a novel immunotherapy avenue for ICC. Our findings reveal a reciprocal dedifferentiation-immunosuppression loop between ICC cells and TAMs, advocating TAM targeting as a promising therapy and highlighting the potential of macrophage modulation in ICC treatment.
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