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

TitleId1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.
Publication TypeJournal Article
Year of Publication2015
AuthorsPapaspyridonos M, Matei I, Huang Y, André Mdo Rosári, Brazier-Mitouart H, Waite JC, Chan AS, Kalter J, Ramos I, Wu Q, Williams C, Wolchok JD, Chapman PB, Peinado H, Anandasabapathy N, Ocean AJ, Kaplan RNatasha, Greenfield JP, Bromberg JF, Skokos D, Lyden DC
JournalNat Commun
Date Published2015 Apr 29
KeywordsAnimals, Cell Differentiation, Disease Progression, Gene Expression Regulation, Neoplastic, Humans, Inhibitor of Differentiation Protein 1, Interferon Regulatory Factors, Leukocytes, Mononuclear, Melanoma, Experimental, Mice, Inbred C57BL, Myeloid Cells, Neoplasm Metastasis, Transforming Growth Factor beta

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.

Custom 1

Alternate JournalNat Commun
PubMed ID25924227
PubMed Central IDPMC4423225
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States

Weill Cornell Medicine Gale and Ira Drukier Institute for Children's Health 413 E. 69th Street New York, NY 10021