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Immunogenic modulation of cholangiocarcinoma cells by chemoimmunotherapy
Shigeo Koido1, Shin Kan2, Kosaku Yoshida3
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan Institute of Clinical Medicine and Research, Jikei University School of Medicine, Tokyo, Japan Department of Oncology, Jikei University School of Medicine, Tokyo, Japan shigeo_koido@jikei.ac.jp.
Background/Aim:
Chemoimmunotherapy has been used to treat intrahepatic cholangiocarcinoma (ICC). However, little is known about the phenomena underlying the immunomodulation of ICC cells elicited by chemoimmunotherapy.
Materials And Methods:
Primary ICC cells from a patient with ICC who received gemcitabine followed by 5-fluorouracil (5-FU), both combined with dendritic cells pulsed with Wilms' tumor 1 (WT1) peptides were cultured. ICC cells were treated with gemcitabine, 5-FU or interferon (IFN)-γ in vitro. The phenotype of the ICC cells was examined by flow cytometry and quantitative reverse transcription polymerase chain reaction.
Results:
Stimulation of the ICC cells with gemcitabine resulted in up-regulation of WT1 mRNA, programmed death receptor ligand-1 (PDL1) and calreticulin. Gemcitabine, 5-FU and IFN-γ induced up-regulation of mucin-1. Moreover, human leukocyte antigen (HLA)-ABC, HLA-DR and PDL1 were extremely up-regulated by IFN-γ.
Conclusion:
Chemoimmunomodulating agents alter the immunogenicity of ICC cells, resulting in complex clinical efficacy results.
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