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. 2025 Jul 13:15:31086.
doi: 10.34172/bi.31086. eCollection 2025.

Targeting immune checkpoints as a new therapeutic strategy for intra-hepatic cholangiocarcinoma

Eman G Khedr  1 , Mariam A Abo Seif  1 , Othman F Abdelzaher  2 , Ahmed B M Mehany  2 , Ola A El-Feky  1
Affiliations

Targeting immune checkpoints as a new therapeutic strategy for intra-hepatic cholangiocarcinoma

Eman G Khedr et al. Bioimpacts. .

Abstract

Introduction: Intrahepatic cholangiocarcinoma (IH-CCA) is a malignancy characterized with limited response to standard chemotherapeutic strategies due to development of drug resistance. We aim to investigate new immune-therapeutic strategy through using AUNP-12 as an immune checkpoint blocker in chemically induced IH-CCA mice model.

Methods: Mice were randomly divided into 2 groups; normal control group and disease group. The disease group was further subdivided into 5 subgroups assigned according to treatment modality. The Immunotherapeutic mechanism of AUNP-12 was investigated through analysis of PD-1/PD-L1 levels and IFN-γ Levels in the tumor microenvironment. Immunohistochemical analysis of CD3+T lymphocytes and TGF-β was performed.

Results: We reported that AUNP-12 significantly decreased levels of PD-1/PD-L1 at the site of tumor with subsequent activation of CD3+T lymphocytes that secrete IFN-γ which specifically lysis tumor cells. AUNP-12 also acts through downregulation of TGF-β signaling in IH-CCA mice group treated with AUNP-12.

Conclusion: Our data indicated that AUNP-12 effectively harbors IH-CCA progression and improves the survival rate of mice. AUNP-12 acts as an immune check point blocker that specifically inhibits PD-1/PD-L1 binding, activates cytotoxic T-lymphocytes, and downregulates TGF-β signaling pathway.

Keywords: Apoptosis; Immune checkpoint blockade; Intra-hepatic cholangiocarcinoma; PD-1/PD-L1; d-Peptide.

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Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

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