title: Immunogenic modulation of cholangiocarcinoma cells by chemoimmunotherapy.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Chemoimmunomodulating agents alter the immunogenicity of ICC cells, resulting in complex clinical efficacy results.
authors.affiliation: Division 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.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koido
authors.affiliation: Department of Oncology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Kan
authors.affiliation: Research and Development Division, Tella Inc., Tokyo, Japan.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Research and Development Division, Tella Inc., Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yoshizaki
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takakura
authors.affiliation: Institute of Clinical Medicine and Research, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Namiki
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Tsukinaga
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Odahara
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Kajihara
authors.affiliation: Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Department of Oncology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ito
authors.affiliation: Research and Development Division, Tella Inc., Tokyo, Japan.
authors.forename: Sei-Ichi
authors.initials: S
authors.lastname: Yusa
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA, U.S.A.
authors.forename: Jianlin
authors.initials: J
authors.lastname: Gong
authors.affiliation: Department of Functional Diagnostic Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ohkusa
authors.affiliation: Department of Oncology, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Sadamu
authors.initials: S
authors.lastname: Homma
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Tajiri
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D001650:Bile Duct Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000951:Antigens, Neoplasm; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D006684:HLA-DR Antigens; D018396:Mucin-1; D012333:RNA, Messenger; D025721:WT1 Proteins; C583751:WT1 protein, human; D003841:Deoxycytidine; D007371:Interferon-gamma; D005472:Fluorouracil; D000093542:Gemcitabine
keywords: 5-fluorouracil; Gemcitabine; IFN-γ; PDL1; WT1; chemoimmunotherapy; immunomodulation