Single administration of low dose cyclophosphamide augments the antitumor effect of dendritic cell vaccine
Single administration of low dose cyclophosphamide augments the antitumor effect of dendritic cell vaccine
复制标题
单次施用低剂量环磷酰胺增强树突状细胞疫苗的抗肿瘤作用
DOI：
10.1007/s00262-007-0305-4
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发表时间：
2007-10-01
影响因子：
5.8
通讯作者：
Zeng, Yi-Xin
中科院分区：
文献类型：
--
作者：
Liu, Ji-Yan;Wu, Yang;Zeng, Yi-Xin
单次给药低剂量环磷酰胺（CTX）先前报道，以提高免疫治疗的抗肿瘤疗效。为了研究这种效应的可能机制，我们研究了单次给予低剂量CTX是否可以增强树突状细胞（DC）疫苗的免疫原性。建立B16黑色素瘤或C26结肠癌肿瘤模型后，小鼠腹腔注射50 mg/kg体重剂量的CTX，4天后接种由小鼠骨髓产生的DC疫苗，并用B16或C26肿瘤细胞裂解物脉冲。CTX处理增强了DC疫苗的抗肿瘤作用，并增加了脾中分泌IFN-γ的淋巴细胞的比例。流式细胞术检测到CTX处理的荷瘤小鼠脾淋巴细胞中CD 4 + CD 25 + FoxP 3+调节性T（Treg）细胞比例显著降低。因此，单次给予低剂量CTX可以通过降低荷瘤小鼠中CD 4 + CD 25 + FoxP 3 + Treg细胞的比例来增强DC疫苗的抗肿瘤免疫应答。我们的研究结果提示了CTX诱导免疫增强的可能机制，并提供了低剂量CTX与DC疫苗联合免疫治疗的策略。
Single administration of low dose cyclophosphamide (CTX) was previously reported to enhance the antitumor efficacy of immunotherapies. To investigate the possible mechanisms for this effect, we examined whether a single administration of low dose CTX could augment the immunogenicity of dendritic cell (DC) vaccines. Fifty milligrams per kilogram body weight dose of CTX was administrated intraperitoneally to mice after B16 melanoma or C26 colon carcinoma tumor models were established, DC vaccine generated from mouse bone marrow and pulsed with B16 or C26 tumor cells lysates were vaccinated 4 days later. CTX treatment potentiated the antitumor effects of the DC vaccine, and increased the proportion of IFN-γ secreting lymphocytes in spleens. Furthermore, a significantly reduced proportion of CD4+CD25+FoxP3+ regulatory T (Treg) cells was detected by flow cytometry in spleen lymphocytes from tumor-bearing mice treated with CTX. Thus, a single administration of low dose CTX could augment antitumor immune responses of DC vaccine by reducing the proportion of CD4+CD25+FoxP3+ Tregcells in tumor-bearing mice. Our results suggested a possible mechanism of CTX-induced immunopotentiation and provided a strategy of immunotherapy combining a low dose CTX with DC vaccine.