Department of Microbiology and Immunology, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-799, South Korea.
Immunobiology. 2010 Mar;215(3):182-93. doi: 10.1016/j.imbio.2009.01.010. Epub 2009 May 22.
As alkylating agents, cyclophosphamides (CTX) are used to treat various cancers and, ironically, to boost immune responses. In the present study, we attempted to elucidate the mechanism responsible for the immunomodulatory effect of high-dose CTX in an established tumor model. A single injection of high-dose CTX increased the survival rate of immunocompetent, but not immunodeficient, mice. Notably, 10 days after CTX injection, the number of CD44(high) memory T cells significantly increased, without a selective decrease in the actual number and percentage of CD4+CD25+Foxp3+ regulatory T cells (Tregs). However, the proportion of Tregs among CD4+ T cells decreased due to expansion of memory and other CD4+ T cell subtypes. This outcome was accompanied by an increase in IL-15 mRNA and up-regulation of IL-15 receptors in the CD44+CD8+ T cell compartment. We postulate that the CTX-induced change in T cell balance may increase anti-tumor immunity.
作为烷化剂，环磷酰胺（CTX）被用于治疗各种癌症，具有讽刺意味的是，它也能增强免疫反应。在本研究中，我们试图阐明高剂量 CTX 在既定肿瘤模型中产生免疫调节作用的机制。单次注射高剂量 CTX 可提高免疫功能正常但免疫缺陷小鼠的存活率。值得注意的是，CTX 注射 10 天后，CD44(high)记忆 T 细胞的数量显著增加，而 CD4+CD25+Foxp3+调节性 T 细胞（Tregs）的实际数量和百分比并没有选择性下降。然而，由于记忆 T 细胞和其他 CD4+T 细胞亚型的扩增，Tregs 在 CD4+T 细胞中的比例下降。这一结果伴随着 CD44+CD8+T 细胞中 IL-15mRNA 的增加和 IL-15 受体的上调。我们推测，CTX 诱导的 T 细胞平衡变化可能会增强抗肿瘤免疫。
