title: Suppressive effects of cyclophosphamide and gemcitabine on regulatory T-cell induction in vitro.
abstract: OBJECTIVE
  Inhibition of CD4(+)FOXP3(+) regulatory T-cell (Treg) activity may be important for successful cancer immunotherapy. We investigated the suppressive effects of several chemotherapeutic agents on Treg induction in vitro.
  
  
  METHODS
  Tregs were induced by incubating human peripheral blood mononuclear cells (PBMCs) with interleukin-2 (500 U/ml) and transforming growth factor-β (10 ng/ml) for four days. PBMCs were simultaneously treated with cyclophosphamide (CPA), gemcitabine (GEM), 5-fluorouracil, levofolinate, or oxaliplatin. Treated PBMCs were examined for CD4 and FOXP3 expression via flow cytometry.
  
  
  RESULTS
  Treg induction was significantly suppressed by treatment with CPA and GEM. The optimal concentration of CPA for Treg suppression was almost identical to the serum levels of patients with cancer, treated with low-dose CPA. Treatment with the other agents did not affect Treg induction.
  
  
  CONCLUSIONS
  Chemotherapy using CPA or GEM may have the potential to augment the antitumor effects of cancer immunotherapy by suppressing Treg induction.
authors.affiliation: Department of Digestive Surgery and Surgical Oncology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-kogushi, Ube city, Yamaguchi Prefecture, 755-8505, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Kan
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hazama
authors.forename: Kazunari
authors.initials: K
authors.lastname: Maeda
authors.forename: Yuka
authors.initials: Y
authors.lastname: Inoue
authors.forename: Sadamu
authors.initials: S
authors.lastname: Homma
authors.forename: Shigeo
authors.initials: S
authors.lastname: Koido
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D003841:Deoxycytidine; D003520:Cyclophosphamide; D000093542:Gemcitabine