中文摘要:
尽管 IL-9 在过继细胞转移治疗中具有强大的抗肿瘤活性,但一些模型表明它可能促进肿瘤生长。在这里,我们展示了 IL-9 信号通路与多种类型肺癌患者的不良预后相关,并且在多种小鼠模型中对肺肿瘤生长是必需的。CD4 T 细胞来源的 IL-9 在肺肿瘤模型中促进 CD11c+ 和 CD11c− 间质巨噬细胞群体的扩增。在机制上,IL-9/巨噬细胞轴需要精氨酸酶 1 (Arg1) 来介导肿瘤生长。事实上,将 Arg1+ 但非 Arg1− 的肺巨噬细胞过继转移至 Il9r−/− 小鼠可促进肿瘤生长。此外,使用巨噬细胞特异性纳米颗粒靶向 IL-9 信号通路可以抑制小鼠肺肿瘤生长。最后,肿瘤病灶中 IL-9R 和 Arg1 的高表达与肺癌患者的不良预后相关。因此,我们的研究表明 IL-9/巨噬细胞/Arg1 轴是肺癌治疗的潜在治疗靶点。
英文摘要:
Although IL-9 has potent anti-tumor activity in adoptive cell transfer therapy, some models suggest that it can promote tumor growth. Here, we show that IL-9 signaling is associated with poor outcomes in patients with various forms of lung cancer, and is required for lung tumor growth in multiple mouse models. CD4+ T cell-derived IL-9 promotes the expansion of both CD11c+ and CD11c− interstitial macrophage populations in lung tumor models. Mechanistically, the IL-9/macrophage axis requires arginase 1 (Arg1) to mediate tumor growth. Indeed, adoptive transfer of Arg1+ but not Arg1- lung macrophages to Il9r−/− mice promotes tumor growth. Moreover, targeting IL-9 signaling using macrophage-specific nanoparticles restricts lung tumor growth in mice. Lastly, elevated expression of IL-9R and Arg1 in tumor lesions is associated with poor prognosis in lung cancer patients. Thus, our study suggests the IL-9/macrophage/Arg1 axis is a potential therapeutic target for lung cancer therapy.
论文信息:
论文题目:Generation, localization and functions of macrophages during the development of testis
期刊名称:Nature Communications
时间期卷:13, Article number: 3811 (2022)
在线时间:2022年7月1日
DOI: doi.org/10.1038/s41467-022-31596-7
产品信息:
货号:C-005
规格:5ml
品牌:Liposoma
产地:荷兰
名称:Clodronate Liposomes
办事处:Target Technology(靶点科技)
Clodronate Liposomes氯膦酸盐脂质体清除肺脏巨噬细胞,荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications:小鼠肺间质巨噬细胞介导IL-9的促肿瘤作用。

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除肺脏巨噬细胞的材料和方法:
Mice were challenged with 150 µl clodronate-containing liposomes (Liposoma, c-005) intravenously followed by 250 μl of fluorescent microspheres (Polysciences, 17154-10) intravenously injected 16–18 h later. GFP+ monocytes were subsequently purified and 1 million cells were injected into recipient mice.
材料和方法文献截图:
