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

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

来源：Nature Communications, 2015, 6(1): 6840.

DOI：10.1038/ncomms7840

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 TGF beta, 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 TGFb 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.

• 出版日期2015-4