Administration of cyclophosphamide changes the immune profile of tumor-bearing mice.
Administration of cyclophosphamide changes the immune profile of tumor-bearing mice.
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DOI：
10.1097/cji.0b013e3181b56af4
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发表时间：
2010-01
期刊：
影响因子：
--
通讯作者：
Hellstrom KE
中科院分区：
文献类型：
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作者：
Liu P;Jaffar J;Hellstrom I;Hellstrom KE
环磷酰胺（CTX）通常用于为更有效的治疗性肿瘤疫苗接种创造“窗口”。根据通常应用的方案，我们向具有来自K1735黑色素瘤SW 1克隆的小（2-3 mm直径）或大（5-7，在一个实验中8-10 mm直径）皮下（sc）生长肿瘤的小鼠腹膜内（ip）注射2 mg CTX，4天后对小鼠实施安乐死，并通过流式细胞术研究脾脏和肿瘤中淋巴细胞的组成。CTX治疗可使CD 3+、CD 4+和CD 8+细胞百分比增加，且肿瘤中的增加显著大于脾脏中的增加，还可使脾脏和肿瘤中的B细胞百分比增加。此外，CTX显著增加了含有IFNγ的肿瘤浸润性CD 4和CD 8细胞、表达NK1.1的细胞以及表达树突状细胞标志物CD 11 c、CD 80和CD 86的细胞的频率，其中在来自小肿瘤小鼠的TIL中增加最多。虽然CTX降低了表达CD 4或CD 8以及CD 25和FoxP 3的TIL的百分比，因此被认为是Treg细胞，但它增加了对Gr 1/CD 11b染色的TIL的频率，Gr 1/CD 11b是MDSC的标志物。我们的结论是，CTX的管理可以有利地影响参与肿瘤排斥反应的几个细胞群。然而，由于CTX对来自直径大于几mm的肿瘤的TIL的作用有限，并且鉴于来自给予CTX的小鼠的TIL中MDSC的百分比增加，因此需要更有效的方法来改善肿瘤疫苗接种。
Cyclophosphamide (CTX) is often used to create a ‘window’ for more effective therapeutic tumor vaccination. According to a commonly applied protocol, we injected 2 mg CTX intraperitoneally (ip) to mice with small (2-3 mm diameter) or large (5-7, and in one experiment 8-10 mm diameter) subcutaneously (sc) growing tumors from the SW1 clone of the K1735 melanoma, euthanized the mice 4 days later and studied the composition of lymphoid cells by flow cytometry in both spleens and tumors. Administration of CTX increased the percentage of CD3+, CD4+ and CD8+ cells with the increases in tumors being significantly greater than in spleens, and it also increased the percentage of B cells in spleens and tumors. Furthermore, CTX dramatically increased the frequency of tumor-infiltrating CD4 and CD8 cells containing IFNγ, of cells expressing NK1.1, and of cells expressing the dendritic cell markers CD11c, CD80 and CD86, with the greatest increases seem among TIL from mice with small tumors. While CTX decreased the percentage of TIL that expressed CD4 or CD8 together with CD25 and FoxP3 and were therefore considered to be Treg cells, it increased the frequency of TIL that stained for Gr1/CD11b, a marker for MDSC. We conclude that administration of CTX can favorably impact several cell populations that are involved in tumor rejection. However, since CTX has a limited effect on TIL from tumors larger than a few mm diameter and in view of an increased percentage of MDSC among TIL from mice given CTX there is a need for more effective ways to improve tumor vaccination.