小鼠肺間質(zhì)巨噬細(xì)胞介導(dǎo)IL-9的促腫瘤作用

中文摘要：

盡管 IL-9 在過繼細(xì)胞轉(zhuǎn)移治療中具有強(qiáng)大的抗腫瘤活性，但一些模型表明它可能促進(jìn)腫瘤生長。在這里，我們展示了 IL-9 信號(hào)通路與多種類型肺癌患者的不良預(yù)后相關(guān)，并且在多種小鼠模型中對(duì)肺腫瘤生長是必需的。CD4 T 細(xì)胞來源的 IL-9 在肺腫瘤模型中促進(jìn) CD11c+ 和 CD11c? 間質(zhì)巨噬細(xì)胞群體的擴(kuò)增。在機(jī)制上，IL-9/巨噬細(xì)胞軸需要精氨酸酶 1 (Arg1) 來介導(dǎo)腫瘤生長。事實(shí)上，將 Arg1+ 但非 Arg1? 的肺巨噬細(xì)胞過繼轉(zhuǎn)移至 Il9r?/? 小鼠可促進(jìn)腫瘤生長。此外，使用巨噬細(xì)胞特異性納米顆粒靶向 IL-9 信號(hào)通路可以抑制小鼠肺腫瘤生長。最后，腫瘤病灶中 IL-9R 和 Arg1 的高表達(dá)與肺癌患者的不良預(yù)后相關(guān)。因此，我們的研究表明 IL-9/巨噬細(xì)胞/Arg1 軸是肺癌治療的潛在治療靶點(diǎn)。

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.

論文信息：

論文題目：Mouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of IL-9

期刊名稱：Nature Communications

時(shí)間期卷：13, Article number: 3811 (2022)

在線時(shí)間：2022年7月1日

DOI： doi.org/10.1038/s41467-022-31596-7

產(chǎn)品信息：

貨號(hào)：C-005

規(guī)格：5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes

辦事處：Target Technology(靶點(diǎn)科技)

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除肺臟巨噬細(xì)胞，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：小鼠肺間質(zhì)巨噬細(xì)胞介導(dǎo)IL-9的促腫瘤作用。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除肺臟巨噬細(xì)胞的材料和方法：

In vivo monocyte/macrophage labeling

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.

材料和方法文獻(xiàn)截圖：