What question did this study set out to answer?

This research aims to identify molecular subtypes of cholangiocarcinoma that correlate with distinct clinical outcomes and therapeutic responses.

April 5, 2026

Abstract 7906: Integrated multi-omics profiling identifies an immunotherapy vulnerable and prognostic associated subtype in cholangiocarcinoma

Key Points

This research aims to identify molecular subtypes of cholangiocarcinoma that correlate with distinct clinical outcomes and therapeutic responses.
Performed integrated multi-omics profiling in 424 CCA patients
Identified four distinct molecular subtypes based on clinical and immunological features
Validated findings with immunohistochemical techniques
Developed a 160-gene classifier for predicting subtypes
Identified four subtypes: C1, C2, C3, and C4 with varying immune characteristics
C3 subtype shows a 75% overall response rate to immune checkpoint blockade
Validated ATP2B1 as a novel prognostic biomarker
C3's response is independent of conventional biomarkers like PD-L1 and TMB

Abstract

Abstract Cholangiocarcinoma (CCA) is an aggressive malignancy with poor prognosis and limited treatment options. This study performed integrated multi-omics profiling as well as immunohistochemical validation on 424 CCA patients, identifying four molecular subtypes with distinct clinical and immunological features: C1 (Proliferative): Driven by *TP53/KRAS* mutations and CpG island methylator phenotype (CIMP+) hypermethylation, showing Th17 cells infiltration and poor outcomes; C2 (Immune-Suppressed MacroLYVE1, (ISMLYVE1) ): Stroma-rich with LYVE1+ macrophages and epithelial-mesenchymal transition (EMT) activation; C3 (Immune-Activated MacroC1QC (ISMC1QC) ): Enriched in C1QC+ macrophages, CD8+ T-cells, and metabolic pathways, highly responsive to immune checkpoint blockade (75% Overall Response Rate (ORR) ) ; C4 (Immune-Excluded, (IE) ): FGFR2-altered and IDH1-mutant, with an immunologically-cold phenotype. We validated ATP2B1 as a novel prognostic biomarker and developed a 160-gene classifier for subtype prediction. The C3 subtype’s exceptional immune checkpoint blockade (ICB) response, independent of conventional biomarkers (PD-L1/microsatellite instability (MSI) /tumor mutational burden (TMB) ), highlights the clinical utility of this classification system in guiding precision immunotherapy for CCA. Citation Format: Lu Chen, Xiangdong Tian. Integrated multi-omics profiling identifies an immunotherapy vulnerable and prognostic associated subtype in cholangiocarcinoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (7 Suppl): Abstract nr 7906.

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Cite This Study

Chen et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fcfda79560c99a0a2bb6 https://doi.org/https://doi.org/10.1158/1538-7445.am2026-7906

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