Suppressive effects of cyclophosphamide and gemcitabine on regulatory T-cell induction in vitro.

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.