T cell- but not tumor cell-produced TGF-β1 promotes the development of spontaneous mammary cancer.
T cell- but not tumor cell-produced TGF-β1 promotes the development of spontaneous mammary cancer.
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DOI：
10.18632/oncotarget.403
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Li MO
中科院分区：
文献类型：
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作者：
Sarkar A;Donkor MK;Li MO
在其发育过程中，肿瘤获得多种能力，使其能够增殖、传播和逃避免疫监视。一种假定的机制是通过细胞因子TGF-β1的产生。我们在最近的研究中表明，T细胞产生的TGF-β1抑制抗肿瘤T细胞反应以促进肿瘤生长，这提出了肿瘤细胞产生的TGF-β1在肿瘤发展中的确切功能的问题。在这里，我们使用乳腺癌的转基因模型，报告从肿瘤细胞中删除TGF-β1并不能保护小鼠免受肿瘤发展。然而，从T细胞去除TGF-β1显著抑制乳腺肿瘤生长。此外，T细胞中TGF-β1的缺乏阻止了肿瘤进展到更高的病理级别，并进一步抑制了肺中的继发性肿瘤发展。这些发现揭示了T细胞而不是肿瘤细胞是促进肿瘤发展的TGF-β1的关键来源。
During their development, tumors acquire multiple capabilities that enable them to proliferate, disseminate and evade immunosurveillance. A putative mechanism is through the production of the cytokine TGF-β1. We showed in our recent studies that T cell-produced TGF-β1 inhibits antitumor T cell responses to foster tumor growth raising the question of the precise function of TGF-β1 produced by tumor cells in tumor development. Here, using a transgenic model of mammary cancer, we report that deletion of TGF-β1 from tumor cells did not protect mice from tumor development. However, ablation of TGF-β1 from T cells significantly inhibited mammary tumor growth. Additionally, absence of TGF-β1 in T cells prevented tumors from advancing to higher pathological grades and further suppressed secondary tumor development in the lungs. These findings reveal T cells but not tumor cells as a critical source of TGF-β1 that promotes tumor development.