Combination therapy with dendritic cells and lenalidomide is an effective approach to enhance antitumor immunity in a mouse colon cancer model.
Combination therapy with dendritic cells and lenalidomide is an effective approach to enhance antitumor immunity in a mouse colon cancer model.
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DOI：
10.18632/oncotarget.15917
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发表时间：
2017-04-18
期刊：
影响因子：
--
通讯作者：
Lee JJ
中科院分区：
文献类型：
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作者：
Vo MC;Nguyen-Pham TN;Lee HJ;Jaya Lakshmi T;Yang S;Jung SH;Kim HJ;Lee JJ
在本研究中，我们观察了来那度胺联合肿瘤抗原负载的树突状细胞(DC)在小鼠结肠癌模型中的疗效。皮下注射MC-38细胞系建立结肠癌荷瘤小鼠。肿瘤生长后，分别于第8、12、16、20天腹腔注射来那度胺(50 mg/kg/d)和肿瘤抗原负载树突状细胞疫苗。肿瘤抗原负载树突状细胞联合来那度胺治疗对肿瘤生长有明显的抑制作用。这些作用与免疫抑制细胞(如髓系抑制细胞和调节性T细胞)的减少、免疫效应细胞(如自然杀伤细胞、CD4+T细胞和CD8+T细胞)的诱导以及细胞毒性T细胞和NK细胞的激活有关。本研究提示，肿瘤抗原负载的DC疫苗联合来那度胺通过抑制免疫抑制细胞的产生和效应细胞的恢复，协同增强小鼠结肠癌模型的抗肿瘤免疫应答，并显示Th1/Th2平衡有利于Th1免疫应答。这种联合DC和来那度胺的方法可能为改善结肠癌的治疗提供一种新的治疗选择。
In this study, we investigated efficacy of lenalidomide in combination with tumor antigen-loaded dendritic cells (DCs) in murine colon cancer model. MC-38 cell lines were injected subcutaneously to establish colon cancer-bearing mice. After tumor growth, lenalidomide (50 mg/kg/day) was injected intraperitoneally on 3 consecutive days in combination with tumor antigen-loaded DC vaccination on days 8, 12, 16, and 20. The tumor antigen-loaded DCs plus lenalidomide combination treatment exhibited a significant inhibition of tumor growth compared with the other groups. These effects were associated with a reduction in immune suppressor cells, such as myeloid-derived suppressor cells and regulatory T cells, with the induction of immune effector cells, such as natural killer cells, CD4+ T cells and CD8+ T cells in spleen, and with the activation of cytotoxic T lymphocytes and NK cells. This study suggests that a combination of tumor antigen-loaded DC vaccination and lenalidomide synergistically enhanced antitumor immune response in the murine colon cancer model, by inhibiting the generation of immune suppressive cells and recovery of effector cells, and demonstrated superior polarization of Th1/Th2 balance in favor of Th1 immune response. This combination approach with DCs and lenalidomide may provide a new therapeutic option to improve the treatment of colon cancer.