The DCDC2/ENO1 axis promotes tumor progression and immune evasion in intrahepatic cholangiocarcinoma via activating FGL1-LAG3 checkpoint

PMCID: PMC12175362

PMID: 40533767

DOI: 10.1186/s13046-025-03436-1

Journal: Journal of experimental & clinical cancer research : CR

Publication Date: 2025-6-18

Authors: Wan W, Li Y, Sun W, Cheng Z, Ma F, et al.

Key Points

• Anti-DCDC2 autoantibodies emerge as a potential novel diagnostic biomarker for intrahepatic cholangiocarcinoma
• DCDC2 promotes ICC progression through complex molecular mechanisms involving ENO1 and FGL1
• The study reveals a new pathway of immune evasion in ICC through the FGL1-LAG3 axis

Summary

This comprehensive study investigates the role of DCDC2 in intrahepatic cholangiocarcinoma (ICC), a challenging malignancy with limited diagnostic and therapeutic options. Utilizing advanced molecular techniques including protein microarrays, transcriptome analysis, and functional assays, researchers discovered that DCDC2 plays a critical role in ICC progression and immune evasion. The study reveals a novel mechanistic pathway where DCDC2 stabilizes ENO1, leading to enhanced AKT phosphorylation and increased FGL1 expression, which ultimately impairs CD8+ T cell functionality.

The research identifies anti-DCDC2 autoantibodies as a promising diagnostic biomarker for ICC, with potential implications for early detection and prognostic assessment. By demonstrating how DCDC2 promotes tumor proliferation, metastasis, and immune evasion, the study provides insights into potential therapeutic targets and mechanisms of ICC progression. The findings are particularly significant given the typically poor prognosis and limited diagnostic methods for this aggressive cancer.