Tumour cell conditioned medium reveals greater M2 skewing of macrophages in the absence of properdin

Tumour cell conditioned medium reveals greater M2 skewing of macrophages in the absence of properdin
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DOI:
10.1002/iid3.142
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发表时间:
2017-03-01
影响因子:
3.2
通讯作者:
Stover, Cordula
Stover, Cordula
中科院分区:
医学4区
文献类型:
--
作者:
Al-Rayahi, Izzat A. M.;Browning, Michael J.;Stover, Cordula

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肿瘤微环境是由近距离存在的免疫细胞、非免疫细胞和肿瘤细胞相互作用形成的。肿瘤细胞引导局部免疫抑制状态的发展,影响抗肿瘤T细胞的活性,为肿瘤发展的逃逸阶段做准备。肿瘤中的巨噬细胞通常发展成所谓的肿瘤相关巨噬细胞,具有独特的活动特征,导致炎症和抗原呈递减少。肿瘤细胞条件培养基对巨噬细胞活性谱依赖于补体成分表达的直接影响尚未被研究。方法:在我们的体外研究中,用同基因肿瘤细胞系B16F10(小鼠黑色素瘤亚系)的条件培养基刺激从properdin缺陷小鼠和野生型小鼠骨髓分化的巨噬细胞。结果:与野生型小鼠的巨噬细胞相比,同源properdin缺陷小鼠的巨噬细胞向M2谱倾斜,包括精氨酸代谢、2型细胞因子产生相关基因的mRNA表达,抗原呈递所需分子的表面表达相对较低。结论:这些数据表明适当的素不足促进肿瘤环境,帮助肿瘤逃避免疫反应。
Introduction: The tumour microenvironment is shaped by the interaction of immune, non immune, and tumour cells present in close proximity. Tumour cells direct the development of a locally immune suppressed state, affecting the activity of anti tumour T cells and preparing the escape phase of tumour development. Macrophages in the tumour typically develop into so-called tumour associated macrophages with a distinct profile of activities which lead to a reduction in inflammation and antigen presentation. The direct impact of tumour cell conditioned medium on the activity profile of macrophages in dependence of their complement component expression has not yet been investigated.Methods: In our in vitro study, macrophages differentiated from bone marrows of properdin deficient and wildtype mice were stimulated with conditioned medium of a syngeneic tumour cell line, B16F10, a mouse melanoma subline.Results: In comparison with macrophages from wildtype mice, those from congenic properdin deficient mice showed skewing towards M2 profile, encompassing mRNA expression for genes involved in arginine metabolism, production of type 2 cytokines, and relatively lower surface expression of molecules needed for antigen presentation.Conclusions: These data suggest that properdin insufficiency promotes a tumour environment that helps the tumour evade the immune response.