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

Nat Commun 2015 Apr 29;6:6840. Epub 2015 Apr 29.

1] Children's Cancer and Blood Foundation Laboratories and Departments of Pediatrics and Cell and Developmental Biology, Weill Cornell Medical College, 413 East 69th Street, New York City, New York 10021, USA [2] Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York City, New York 10065, USA.

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.

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http://dx.doi.org/10.1038/ncomms7840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423225PMC
April 2015
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