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 () and David Lyden ()
Additional contact information
Marianna Papaspyridonos: Weill Cornell Medical College
Irina Matei: Weill Cornell Medical College
Yujie Huang: Weill Cornell Medical College
Maria do Rosario Andre: Weill Cornell Medical College
Helene Brazier-Mitouart: Weill Cornell Medical College
Janelle C. Waite: Regeneron Pharmaceuticals
April S. Chan: Weill Cornell Medical College
Julie Kalter: Regeneron Pharmaceuticals
Ilyssa Ramos: Regeneron Pharmaceuticals
Qi Wu: Regeneron Pharmaceuticals
Caitlin Williams: Weill Cornell Medical College
Jedd D. Wolchok: Melanoma and Immunotherapy Service, Memorial Sloan Kettering Cancer Center
Paul B. Chapman: Memorial Sloan Kettering Cancer Center
Hector Peinado: Weill Cornell Medical College
Niroshana Anandasabapathy: Brigham and Women’s Hospital, Harvard Medical School
Allyson J. Ocean: Weill Cornell Medical College and Medical Oncology/Solid Tumor Program
Rosandra N. Kaplan: Center for Cancer Research, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health
Jeffrey P. Greenfield: Weill Cornell Medical College
Jacqueline Bromberg: Memorial Sloan Kettering Cancer Center
Dimitris Skokos: Regeneron Pharmaceuticals
David Lyden: Weill Cornell Medical College

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7840

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