CD206-positive myeloid cells bind galectin-9 and promote a tumor-supportive microenvironment.
CD206-positive myeloid cells bind galectin-9 and promote a tumor-supportive microenvironment.
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DOI：
10.1002/path.5093
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Markovic SN
中科院分区：
文献类型：
--
作者：
Enninga EAL;Chatzopoulos K;Butterfield JT;Sutor SL;Leontovich AA;Nevala WK;Flotte TJ;Markovic SN
在转移性黑色素瘤患者中，血液中高水平的半乳糖凝集素-9与较差的总生存率和偏向于支持肿瘤生长的Th2炎症状态相关。虽然已经描述了半乳糖凝集素-9通过T细胞上的TIM3信号传导，但对半乳糖凝集素-9与巨噬细胞的相互作用知之甚少。我们的目的是确定半乳糖凝集素-9是否是巨噬细胞上CD206的结合伙伴，以及这种相互作用的结果是否具有肿瘤支持作用。我们确定CD68+巨噬细胞与半乳糖凝集素-9或抗CD206孵育可阻断靶标结合，并且通过细胞裂解物的免疫沉淀检测CD206和半乳糖凝集素-9。CD206与半乳糖凝集素-9的结合亲和力为280 nM。半乳糖凝集素-9导致CD206+巨噬细胞显著增加FGF2和单核细胞趋化蛋白（MCP-1），但减少巨噬细胞来源的趋化因子（MDC）。半乳糖凝集素-9对经典单核细胞亚群没有影响，但引起非经典群体的扩大。最后，肿瘤中CD206巨噬细胞数量的增加与半凝集素-9的表达呈正相关，高水平的CD206巨噬细胞与黑色素瘤的存活呈负相关。这些结果表明，半凝集素-9结合CD206在M2巨噬细胞上，这似乎驱动血管生成和产生支持肿瘤生长和不良患者预后的趋化因子。因此，通过循环单核细胞系统地靶向这种相互作用可能是一种提高巨噬细胞局部抗肿瘤作用的新方法。
In patients with metastatic melanoma, high blood levels of galectin-9 are correlated with worse overall survival and a bias towards a Th2 inflammatory state supportive of tumor growth. Although galectin-9 signaling through TIM3 on T cells has been described, less is known about the interaction of galectin-9 with macrophages. We aimed to determine whether galectin-9 is a binding partner of CD206 on macrophages and whether the result of this interaction is tumor-supportive. It was determined that incubation of CD68+ macrophages with galectin-9 or anti-CD206 blocked target binding and that both CD206 and galectin-9 were detected by immunoprecipitation of cell lysates. CD206 and galectin-9 had a binding affinity of 280 nM. Galectin-9 causes CD206+ macrophages to make significantly more FGF2 and monocyte chemoattractant protein (MCP-1), but less macrophage-derived chemokine (MDC). Galectin-9 had no effect on classical monocyte subsets, but caused expansion of the non-classical populations. Lastly, there was a positive correlation between increasing numbers of CD206 macrophages and galectin-9 expression in tumors, and high levels of CD206 macrophages correlated negatively with melanoma survival. These results indicate that galectin-9 binds CD206 on M2 macrophages, which appear to drive angiogenesis and the production of chemokines that support tumor growth and poor patient prognoses. Targeting this interaction systemically through circulating monocytes may therefore be a novel way to improve local anti-tumor effects by macrophages.
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DOI：
10.1084/jem.20132687
发表时间：
2014-06-30
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Madireddi S;Eun SY;Lee SW;Nemčovičová I;Mehta AK;Zajonc DM;Nishi N;Niki T;Hirashima M;Croft M
通讯作者：
Croft M
影响因子：
4.8
作者：
Nagae, Masamichi;Nishi, Nozomu;Kato, Ryuichi
通讯作者：
Kato, Ryuichi
DOI：
10.1016/j.urolonc.2017.02.008
发表时间：
2017-06-01
影响因子：
2.7
作者：
Liu, Yidong;Liu, Zheng;Xu, Jiejie
通讯作者：
Xu, Jiejie
影响因子：
8.8
作者：
Guthrie GJ;Roxburgh CS;Farhan-Alanie OM;Horgan PG;McMillan DC
通讯作者：
McMillan DC
影响因子：
2.2
作者：
Enninga EA;Nevala WK;Holtan SG;Leontovich AA;Markovic SN
通讯作者：
Markovic SN