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

Marianna Papaspyridonos, Irina Matei, Yujie Huang, Maria do Rosario Andre, Helene Brazier-Mitouart, Janelle C. Waite, April S. Chan, Julie Kalter, Ilyssa Ramos, Qi Wu, Caitlin Williams, Jedd D. Wolchok, Paul B. Chapman, Hector Peinado, Niroshana Anandasabapathy, Allyson J. Ocean, Rosandra N. Kaplan, Jeffrey P. Greenfield, Jacqueline Bromberg, Dimitris Skokos & 1 others David Lyden

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Abstract

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.

Original languageEnglish
Article number6840
Pages (from-to)Online
Number of pages13
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 29 Apr 2015

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Keywords

  • SELF-RENEWAL CAPACITY
  • REGULATORY T-CELLS
  • TGF-BETA
  • DENDRITIC CELLS
  • PERIPHERAL-BLOOD
  • PROGENITOR CELLS
  • CANCER-PATIENTS
  • DIFFERENTIATION
  • PROTEINS
  • MELANOMA

Cite this

Papaspyridonos, M., Matei, I., Huang, Y., Andre, M. D. R., Brazier-Mitouart, H., Waite, J. C., ... Lyden, D. (2015). Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation. Nature Communications, 6, Online. [6840]. https://doi.org/10.1038/ncomms7840