Abstract
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.
Keywords:
5-fluorouracil; Gemcitabine; IFN-γ; PDL1; WT1; chemoimmunotherapy; immunomodulation.
Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Neoplasm / immunology
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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B7-H1 Antigen / genetics
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B7-H1 Antigen / metabolism
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Bile Duct Neoplasms / immunology
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Bile Duct Neoplasms / pathology
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Bile Duct Neoplasms / therapy*
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Bile Ducts, Intrahepatic / drug effects
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Bile Ducts, Intrahepatic / immunology*
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Bile Ducts, Intrahepatic / pathology
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Cholangiocarcinoma / immunology
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Cholangiocarcinoma / pathology
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Cholangiocarcinoma / therapy*
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Combined Modality Therapy
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Dendritic Cells / immunology*
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Deoxycytidine / administration & dosage
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Deoxycytidine / analogs & derivatives
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Female
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Fluorouracil / administration & dosage
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Gemcitabine
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HLA-DR Antigens / genetics
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HLA-DR Antigens / metabolism
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Humans
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Immunotherapy*
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Interferon-gamma / administration & dosage
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Lymphatic Metastasis
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Middle Aged
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Mucin-1 / genetics
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Mucin-1 / metabolism
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Peritoneal Neoplasms / immunology
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Peritoneal Neoplasms / secondary
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Peritoneal Neoplasms / therapy
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Cells, Cultured
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WT1 Proteins / genetics
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WT1 Proteins / metabolism
Substances
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Antigens, Neoplasm
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B7-H1 Antigen
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CD274 protein, human
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HLA-DR Antigens
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Mucin-1
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RNA, Messenger
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WT1 Proteins
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WT1 protein, human
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Deoxycytidine
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Interferon-gamma
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Fluorouracil
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Gemcitabine