Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, PR China.
Int Immunopharmacol. 2012 Feb;12(2):425-32. doi: 10.1016/j.intimp.2011.12.016. Epub 2012 Jan 4.
It has been reported that treatment with cyclophosphamide (CTX) as a chemotherapeutic drug in cancer patients or tumor-bearing mice can result in an increase in the proportion of myeloid derived suppressor cells (MDSCs) in blood and lymphoid organs. Here we sought to clarify the possible mechanism of this unwanted increase in proportion of MDSCs in tumor-bearing mice after CTX treatment. We found that both CD4(+) T cells and CD8(+) T cells underwent an expansion and activation before the increase of MDSCs in the early period of CTX treatment in 4T1 breast tumor-bearing mice. The proportion of MDSCs in nude mice lacking T cells after CTX therapy was comparable to that in nude mice without CTX treatment. T cell transfer to 4T1-bearing nude mice enhanced the proportion of MDSCs in tumor-bearing mice after CTX therapy. The co-culture of MDSCs and T cells in vitro also showed that CD4(+) T cells and CD8(+) T cells could facilitate the expansion and survival of MDSCs, and this effect was mediated by IFN-γ released by T cells. These results gave an explanation of the unwanted consequence resulted from CTX treatment in tumor-bearing mice. It also provided some insights into the strategies for eliminating the bad side of CTX treatment and to make it more effective in cancer therapy.
据报道，在癌症患者或荷瘤小鼠中使用环磷酰胺（CTX）作为化疗药物治疗会导致血液和淋巴器官中髓系来源抑制细胞（MDSC）的比例增加。在这里，我们试图阐明 CTX 治疗后荷瘤小鼠中 MDSC 比例增加的可能机制。我们发现，在 CTX 治疗的早期，4T1 乳腺癌荷瘤小鼠中 MDSC 增加之前，CD4(+)T 细胞和 CD8(+)T 细胞就经历了扩增和激活。CTX 治疗后缺乏 T 细胞的裸鼠中 MDSC 的比例与未接受 CTX 治疗的裸鼠相似。将 T 细胞转移到 4T1 荷瘤裸鼠中会增强 CTX 治疗后荷瘤小鼠中 MDSC 的比例。MDSC 和 T 细胞的体外共培养也表明 CD4(+)T 细胞和 CD8(+)T 细胞可以促进 MDSC 的扩增和存活，这种作用是由 T 细胞释放的 IFN-γ介导的。这些结果解释了 CTX 治疗荷瘤小鼠所带来的不良后果。它还为消除 CTX 治疗的不良影响并使其在癌症治疗中更有效提供了一些思路。
