Immunogenic modulation of cholangiocarcinoma cells by chemoimmunotherapy

Anticancer Res. 2014 Nov;34(11):6353-61.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Bile Duct Neoplasms / immunology
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / therapy*
  • Bile Ducts, Intrahepatic / drug effects
  • Bile Ducts, Intrahepatic / immunology*
  • Bile Ducts, Intrahepatic / pathology
  • Cholangiocarcinoma / immunology
  • Cholangiocarcinoma / pathology
  • Cholangiocarcinoma / therapy*
  • Combined Modality Therapy
  • Dendritic Cells / immunology*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Fluorouracil / administration & dosage
  • Gemcitabine
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / metabolism
  • Humans
  • Immunotherapy*
  • Interferon-gamma / administration & dosage
  • Lymphatic Metastasis
  • Middle Aged
  • Mucin-1 / genetics
  • Mucin-1 / metabolism
  • Peritoneal Neoplasms / immunology
  • Peritoneal Neoplasms / secondary
  • Peritoneal Neoplasms / therapy
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • WT1 Proteins / genetics
  • WT1 Proteins / metabolism

Substances

  • Antigens, Neoplasm
  • B7-H1 Antigen
  • CD274 protein, human
  • HLA-DR Antigens
  • Mucin-1
  • RNA, Messenger
  • WT1 Proteins
  • WT1 protein, human
  • Deoxycytidine
  • Interferon-gamma
  • Fluorouracil
  • Gemcitabine