Suppressive effects of cyclophosphamide and gemcitabine on regulatory T-cell induction in vitro.
Suppressive effects of cyclophosphamide and gemcitabine on regulatory T-cell induction in vitro.
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发表时间：
2012-12
影响因子：
2
通讯作者：
Shi-feng Kan;S. Hazama;K. Maeda;Y. Inoue;S. Homma;S. Koido;M. Okamoto;M. Oka
中科院分区：
文献类型：
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作者：
Shi-feng Kan;S. Hazama;K. Maeda;Y. Inoue;S. Homma;S. Koido;M. Okamoto;M. Oka
背景/目的 抑制 CD4(+)FOXP3(+) 调节性 T 细胞 (Treg) 活性对于成功的癌症免疫治疗可能很重要。我们研究了几种化疗药物对体外 Treg 诱导的抑制作用。材料和方法 通过将人外周血单核细胞 (PBMC) 与白介素-2 (500 U/ml) 和转化生长因子-β (10 ng/ml) 一起孵育四天来诱导 Tregs。同时用环磷酰胺 (CPA)、吉西他滨 (GEM)、5-氟尿嘧啶、左亚叶酸或奥沙利铂处理 PBMC。通过流式细胞术检查处理后的 PBMC 的 CD4 和 FOXP3 表达。结果 CPA 和 GEM 治疗显着抑制了 Treg 诱导。抑制 Treg 的 CPA 最佳浓度几乎与接受低剂量 CPA 治疗的癌症患者的血清水平相同。其他药物治疗不影响 Treg 诱导。结论 使用 CPA 或 GEM 的化疗可能通过抑制 Treg 诱导来增强癌症免疫疗法的抗肿瘤作用。
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.