The abstract is read at the publisher; the summary is JClub's.
STP-high intrahepatic cholangiocarcinoma (iCCA) tumors—quantified by a squamous transition potential index—are linked to ASC-like dismal outcomes in about 20-30% of patients.
- Why it matters: Adenosquamous carcinoma in iCCA is rare (~1-2%) but signals lethal progression, and clinicians lack a way to identify and therapeutically target the latent squamous program behind it.
- What they did: The study defines latent squamous plasticity as a transcriptionally primed, histology-silent state measured by STP, then tests mechanisms involving FOSL1 and p63 and runs a drug-repurposing screen.
- The result: FOSL1 reshapes chromatin to drive a squamous program and, via PTGS2/COX-2–linked PGE2, promotes neutrophil-mediated FOXP3-negative Tr1 polarization that predicts immunotherapy resistance; celecoxib counteracts this and is in a phase Ib/II trial (NCT07632235).
The findingWhy it mattersWhat they didThe result
AI summary of the abstract · may contain errors · not medical advice · read the paper.