A central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.

中文翻译：

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Id1通过削弱髓样细胞的成熟来抑制抗肿瘤免疫反应并促进肿瘤进展。

肿瘤进展和转移的主要机制涉及部分通过肿瘤分泌因子介导的免疫抑制性“宏环境”的产生。在这里，我们证明了对肿瘤衍生因子（例如TGFβ）的分化抑制剂1（Id1）的上调负责在肿瘤进展过程中从树突状细胞（DC）分化转变为髓样抑制细胞的扩增。Id1的遗传失活在很大程度上纠正了髓样失衡，而在没有肿瘤衍生因子的情况下Id1的过表达会重新创建它。Id1的过表达通过下调参与DC分化的​​关键分子和抑制CD8 T细胞增殖来导致系统性免疫抑制，从而促进原发性肿瘤的生长和转移进程。此外，晚期黑色素瘤患者血浆TGFβ水平升高，并在髓样外周血细胞中表达更高的ID1水平。这项研究揭示了Id1在抑制肿瘤进展和转移过程中的抗肿瘤免疫反应中的关键作用。