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Reprogramming Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances

Jiang Chen¹, Zohreh Amoozgar¹, Xin Liu^1,2

¹Edwin. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School; 100 Blossom Street, Cox-734, MA 02114, USA.

Biorxiv : the Preprint Server for Biology

|February 7, 2023

Summary

Combining gemcitabine/cisplatin chemotherapy with dual immune checkpoint blockade (anti-PD1 and anti-CTLA-4) significantly improves survival in aggressive intrahepatic cholangiocarcinoma (ICC) models by enhancing T-cell responses.

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Area of Science:

Hepatobiliary cancers
Immunotherapy
Cancer immunology

Background:

Intrahepatic cholangiocarcinoma (ICC) presents limited treatment options and poor prognosis.
Current anti-PD-L1 immunotherapy combined with gemcitabine/cisplatin shows efficacy in biliary tract cancers, but benefits only a subset of patients.

Conclusions:

Gemcitabine/cisplatin chemotherapy enhances the efficacy of anti-PD1/CTLA-4 immunotherapy in aggressive ICC by normalizing vasculature and increasing T-cell infiltration.
Rational scheduling of ICB with chemotherapy can optimize treatment outcomes and reduce drug exposure.
This combination strategy warrants clinical investigation for ICC patients resistant to current therapies.