Multiple-omics analysis reveals a dedifferentiation-immune loop in intrahepatic cholangiocarcinoma.

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 IC

SUBMITTER: Ruan J 

PROVIDER: S-EPMC11997497 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature