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

Authors: Papaspyridonos, M.; Matei, I.; Huang, Y.; Do Rosario Andre, M.; Brazier-Mitouart, H.; Waite, J. C.; Chan, A. S.; Kalter, J.; Ramos, I.; Wu, Q.; Williams, C.; Wolchok, J. D.; Chapman, P. B.; Peinado, H.; Anandasabapathy, N.; Ocean, A. J.; Kaplan, R. N.; Greenfield, J. P.; Bromberg, J.; Skokos, D.; Lyden, D.
Article Title: Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation
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. © 2015 Macmillan Publishers Limited. All rights reserved.
Keywords: controlled study; primary tumor; gene deletion; advanced cancer; nonhuman; cancer patient; flow cytometry; colorectal cancer; cd8+ t lymphocyte; cell proliferation; animal cell; mouse; gene overexpression; gene expression; gene expression profiling; cell maturation; steady state; inhibitor of differentiation 1; transforming growth factor beta; animal experiment; animal model; cell differentiation; blood; regulatory t lymphocyte; immune response; quantitative analysis; lentivirus vector; interleukin 6; tumor immunity; cytokine production; gene inactivation; real time polymerase chain reaction; upregulation; bone marrow cell; osteogenic protein 1; tumor growth; tumor; breast adenocarcinoma; immunosuppressive treatment; breast metastasis; fluorescence activated cell sorting; myeloid progenitor cell; plasma; cell organelle; suppressor cell; peripheral blood mononuclear cell; cd31 antigen; spleen cell; metastatic melanoma; maturation; cancer; human; article
Journal Title: Nature Communications
Volume: 6
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2015-04-29
Start Page: 6840
Language: English
DOI: 10.1038/ncomms7840
PROVIDER: scopus
PMCID: PMC4423225
PUBMED: 25924227
Notes: Export Date: 3 June 2015 -- Source: Scopus
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MSK Authors
  1. David C Lyden
    83 Lyden
  2. Jedd D Wolchok
    656 Wolchok
  3. Paul Chapman
    246 Chapman