Blood monocytes from mammary tumor-bearing mice: Early targets of tumor-induced immune suppression?
Blood monocytes from mammary tumor-bearing mice: Early targets of tumor-induced immune suppression?
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DOI：
10.3892/ijo_00000740
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发表时间：
2010-10-01
影响因子：
5.2
通讯作者：
Torroella-Kouri, Marta
中科院分区：
文献类型：
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作者：
Caso, Raul;Silvera, Risset;Torroella-Kouri, Marta
我们先前已经表明，来自携带晚期D1-DMBA 3乳腺肿瘤的小鼠的腹腔巨噬细胞的炎症功能受损，但也没有被交替激活，并且比来自正常小鼠的腹腔巨噬细胞分化更少。然而，很少有人知道类似的缺陷是否存在于其前体阶段的血液单核细胞。我们检查了来自乳腺肿瘤荷瘤小鼠的血液单核细胞在成为巨噬细胞之前是否已经改变了其活化谱，以及它们是否对应于炎症或常驻单核细胞亚型。目前，许多努力致力于逆转肿瘤宿主中的巨噬细胞不利性状;由于这些细胞驻留在组织内，因此访问受到限制。血液单核细胞可以更好地靶向和操作的侵入性较小的手段。在本研究中，从D1-DMBA-3乳腺癌荷瘤和正常BALB/c小鼠的全血中分离单个核细胞，并分析CD 115（+）单核细胞。我们的研究结果表明，在肿瘤宿主中，循环单核细胞增加;这些单核细胞表现出几种髓系分化标志物（如CD 115、F4/80、CD 68和CD 11b）的表达减少。此外，在这些细胞中观察到MHC II、CD 62 L和促血管生成标记物Tie-2的下调，而Gr-1和Ly 6C上调。此外，首次在肿瘤宿主血液单核细胞中进行的基因微阵列分析表明，它们表达促炎和抗炎细胞因子和趋化因子的混合物。有趣的是，CCR 2和CX 3CR 1，这是至关重要的单核细胞定义为炎症或居民，分别，都上调。重要的是，补体蛋白增强，而一氧化氮的产生减少，并且在这些细胞中检测不到可测量的辅酶A酶活性。总的来说，我们的研究代表了对荷瘤小鼠血液单核细胞的第一次全面分析;我们得出结论，这些细胞既不完全是炎症性的，也不完全是抑制性的，并且分化程度较低，类似于它们后来成为的巨噬细胞。
We have previously shown that peritoneal macrophages from mice bearing advanced D1-DMBA3 mammary tumors are impaired in their inflammatory functions but are not alternatively activated either and are less differentiated than the ones from normal mice. However, little is known about whether similar defects exist in their precursor stages as blood monocytes. We examined if blood monocytes from mammary tumor-bearing mice are already altered in their activation profiles before becoming macrophages and whether they correspond to inflammatory or resident monocyte sub-types. Much effort is currently devoted to reversing macrophage adverse traits in tumor hosts; as these cells reside within tissues, access is limited. Blood monocytes could be better targeted and manipulated by less invasive means. In the present study, mononuclear cells were isolated from whole blood of D1-DMBA-3 mammary tumor-bearing and normal BALB/c mice and CD115(+) monocytes were analyzed. Our results show that there is an increase in circulating monocytes in tumor hosts; these monocytes exhibit a reduced expression of several myeloid differentiation markers such as CD115, F4/80, CD68 and CD11b. Moreover, downregulation of MHC II, CD62L and the proangiogenic marker Tie-2 are observed in these cells, whereas Gr-1 and Ly6C are upregulated. Furthermore, gene microarray analysis performed for the first time in blood monocytes from tumor hosts indicates that they express a mixture of pro-inflammatory and anti-inflammatory cytokines and chemokines. Interestingly, CCR2 and CX3CR1, which are crucial in monocyte definition as inflammatory or resident, respectively, are both upregulated. Importantly, complement proteins are enhanced whereas nitric oxide production is decreased and there is no measurable arginase activity detected in these cells. Collectively, our study represents the first comprehensive analysis of blood monocytes from tumor-bearing mice; we conclude that these cells are neither completely inflammatory nor suppressive and are less differentiated, similar to the macrophages they later become.