中文摘要:
盡管 IL-9 在過(guò)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(zhǎng)。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(zhǎng)是必需的。CD4 T 細(xì)胞來(lái)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(lái)介導(dǎo)腫瘤生長(zhǎng)。事實(shí)上,將 Arg1+ 但非 Arg1? 的肺巨噬細(xì)胞過(guò)繼轉(zhuǎn)移至 Il9r?/? 小鼠可促進(jìn)腫瘤生長(zhǎng)。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(zhǎng)。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:
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:


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