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Publication : Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.

First Author  Papaspyridonos M Year  2015
Journal  Nat Commun Volume  6
Pages  6840 PubMed ID  25924227
Mgi Jnum  J:222777 Mgi Id  MGI:5645592
Doi  10.1038/ncomms7840 Citation  Papaspyridonos M, et al. (2015) Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation. Nat Commun 6:6840
abstractText  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 TGFbeta, 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 TGFbeta 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.
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