Small Duct and Large Duct Type Intrahepatic Cholangiocarcinoma Reveal Distinct Patterns of Immune Signatures

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2024 Jul 21

PMID 39034327

Authors

Simon Bernatz

Falko Schulze

Julia Bein

Katrin Bankov

Scherwin Mahmoudi

Leon D Grunewald

Vitali Koch

Angelika Stehle

Andreas A Schnitzbauer

Dirk Walter

Fabian Finkelmeier

Stefan Zeuzem

Thomas J Vogl

Peter J Wild

Maximilian N Kinzler

Affiliations

Soon will be listed here.

Abstract

Purpose: Dedicated gene signatures in small (SD-iCCA) and large (LD-iCCA) duct type intrahepatic cholangiocarcinoma remain unknown. We performed immune profiling in SD- and LD-iCCA to identify novel biomarker candidates for personalized medicine.

Methods: Retrospectively, 19 iCCA patients with either SD-iCCA (n = 10, median age, 63.1 years (45-86); men, 4) or LD-iCCA (n = 9, median age, 69.7 years (62-85); men, 5)) were included. All patients were diagnosed and histologically confirmed between 04/2009 and 01/2021. Tumor tissue samples were processed for differential expression profiling using NanoString nCounter® PanCancer Immune Profiling Panel.

Results: With the exception of complement signatures, immune-related pathways were broadly downregulated in SD-iCCA vs. LD-iCCA. A total of 20 immune-related genes were strongly downregulated in SD-iCCA with DMBT1 (log2fc = -5.39, p = 0.01) and CEACAM6 (log2fc = -6.38, p = 0.01) showing the strongest downregulation. Among 7 strongly (log2fc > 2, p ≤ 0.02) upregulated genes, CRP (log2fc = 5.06, p = 0.02) ranked first, and four others were associated with complement (C5, C4BPA, C8A, C8B). Total tumor-infiltrating lymphocytes (TIL) signature was decreased in SD-iCCA with elevated ratios of exhausted-CD8/TILs, NK/TILs, and cytotoxic cells/TILs while having decreased ratios of B-cells/TILs, mast cells/TILs and dendritic cells/TILs. The immune profiling signatures in SD-iCCA revealed downregulation in chemokine signaling pathways inclulding JAK2/3 and ERK1/2 as well as nearly all cytokine-cytokine receptor interaction pathways with the exception of the CXCL1/CXCR1-axis.

Conclusion: Immune patterns differed in SD-iCCA versus LD-iCCA. We identified potential biomarker candidate genes, including CRP, CEACAM6, DMBT1, and various complement factors that could be explored for augmented diagnostics and treatment decision-making.

Citing Articles

New Relevant Evidence in Cholangiocarcinoma Biology and Characterization.

Porro N, Spinola-Lasso E, Pastore M, Caligiuri A, Di Tommaso L, Marra F Cancers (Basel). 2025; 16(24.

PMID: 39766138 PMC: 11674836. DOI: 10.3390/cancers16244239.

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