Author
Listed:
- Marianna Papaspyridonos
(Weill Cornell Medical College
Present address: Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA)
- Irina Matei
(Weill Cornell Medical College)
- Yujie Huang
(Weill Cornell Medical College
Weill Cornell Medical College)
- Maria do Rosario Andre
(Weill Cornell Medical College
Oncology and Human Toxicology, Faculdade de Ciência Médicas, Universidade Nova de Lisboa)
- 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
Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center)
- Paul B. Chapman
(Memorial Sloan Kettering Cancer Center)
- Hector Peinado
(Weill Cornell Medical College
Tumor Metastasis Laboratory, Fundación Centro Nacional de Investigaciones Oncológicas)
- 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
Memorial Sloan Kettering Cancer Center)
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.
Suggested Citation
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 & Jed, 2015.
"Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation,"
Nature Communications, Nature, vol. 6(1), pages 1-13, November.
Handle:
RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7840
DOI: 10.1038/ncomms7840
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