Genomic and immune profiling characterizes immune heterogeneity and a TIGIT-associated subtype in intrahepatic cholangiocarcinoma.

@article{korosteleva2026genomic,
  title = {{Genomic and immune profiling characterizes immune heterogeneity and a TIGIT-associated subtype in intrahepatic cholangiocarcinoma.}},
  author = {Anastasiia Korosteleva and Josephine Sophie Reschke and Dawei Yi and Silke Marhenke and Jinbo Zhao and Valery Volk and Tanja Reineke-Plaaß and Simon Peter and Charlotte Hoffmann and Doan Duy Hai Tran and Christoph Gerdes and Melanie Bathon and Walter Kolch and Friedrich Feuerhake and Vadim Zhernovkov and Anna Saborowski and Arndt Vogel},
  journal = {Hepatology communications},
  year = {2026},
  month = oct,
  doi = {10.1097/hc9.0000000000001052},
  url = {https://europepmc.org/article/MED/42900155},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Genomic and immune profiling characterizes immune heterogeneity and a TIGIT-associated subtype in intrahepatic cholangiocarcinoma.
AU  - Anastasiia Korosteleva
AU  - Josephine Sophie Reschke
AU  - Dawei Yi
AU  - Silke Marhenke
AU  - Jinbo Zhao
AU  - Valery Volk
AU  - Tanja Reineke-Plaaß
AU  - Simon Peter
AU  - Charlotte Hoffmann
AU  - Doan Duy Hai Tran
AU  - Christoph Gerdes
AU  - Melanie Bathon
AU  - Walter Kolch
AU  - Friedrich Feuerhake
AU  - Vadim Zhernovkov
AU  - Anna Saborowski
AU  - Arndt Vogel
PY  - 2026
DA  - 2026/10/19
JO  - Hepatology communications
DO  - 10.1097/hc9.0000000000001052
UR  - https://europepmc.org/article/MED/42900155
AB  - Background  Intrahepatic cholangiocarcinoma (iCCA) is characterized by marked molecular and microenvironmental heterogeneity and moderate response to immunotherapy. We aimed to define the genomic and spatial determinants of immune checkpoint activity in iCCA and their association with clinical outcome.Methods  We performed integrated transcriptomic, DNA panel sequencing, and multiplex immunohistochemistry analyses in a cohort of 144 patients with iCCA. Tumors were classified according to STIM-defined microenvironmental subtypes. Spatially resolved immune profiling was conducted across the tumor core, stroma, invasive margin, and adjacent liver. Immune checkpoint expression, cellular proximity, and clinical outcome were analyzed using Cox regression and Kaplan-Meier methods. TIGIThigh tumors were further characterized by differential gene expression and pathway enrichment analyses.ResultsSTIM classification stratified tumors into inflamed (47%) and non-inflamed (53%) subtypes with distinct survival outcomes and genomic profiles. Recurrent alterations in CDKN2A/B, TP53, MTAP, and BAP1 showed subtype-specific enrichment and prognostic relevance. Spatial immune profiling revealed compartment-specific distributions of T cells and immune checkpoints, with predominance of TIGIT and PD-1 expression in stromal and marginal regions. Most tumor-infiltrating T cells lacked inhibitory receptor expression, while co-expression of multiple checkpoints was uncommon. TIGIThigh tumors displayed coordinated activation of immune effector, antigen presentation, and interferon signaling pathways, alongside enrichment of distinct genomic alterations, defining an immune-activated molecular subtype.Conclusion  Integrated genomic and spatial immune profiling reveals pronounced context-dependent heterogeneity of immune checkpoint regulation in iCCA. TIGIT delineates an immune-activated subtype with distinct molecular features, providing a potential biomarker framework for patient stratification and rational immunotherapeutic targeting.
SN  - 2471-254X
ER  -