Document Detail


Suppressive effects of cyclophosphamide and gemcitabine on regulatory T-cell induction in vitro.
MedLine Citation:
PMID:  23225438     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIM: 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.
MATERIALS AND 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.
CONCLUSION: Chemotherapy using CPA or GEM may have the potential to augment the antitumor effects of cancer immunotherapy by suppressing Treg induction.
Authors:
Shin Kan; Shoichi Hazama; Kazunari Maeda; Yuka Inoue; Sadamu Homma; Shigeo Koido; Masato Okamoto; Masaaki Oka
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  32     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-05-02     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  5363-9     Citation Subset:  IM    
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.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Cells, Cultured
Cyclophosphamide / pharmacology*
Deoxycytidine / analogs & derivatives*,  pharmacology
Dose-Response Relationship, Drug
Forkhead Transcription Factors / biosynthesis,  immunology
Humans
Immunosuppressive Agents / pharmacology*
Leukocytes, Mononuclear / drug effects,  immunology
T-Lymphocytes, Regulatory / drug effects*,  immunology
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/FOXP3 protein, human; 0/Forkhead Transcription Factors; 0/Immunosuppressive Agents; 50-18-0/Cyclophosphamide; 951-77-9/Deoxycytidine; B76N6SBZ8R/gemcitabine

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