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Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression

Title
Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression
Authors
Chen, LimoGibbons, Don L.Goswami, SangeetaCortez, Maria AngelicaAhn, Young-HoByers, Lauren A.Zhang, XuejunYi, XiaohuiDwyer, DavidLin, WeiDiao, LixiaWang, JingRoybal, Jonathon D.Patel, MayuriUngewiss, ChristinPeng, DavidAntonia, ScottMediavilla-Varela, MelanieRobertson, GordonJones, SteveSuraokar, MilindWelsh, James W.Erez, BaruchWistuba, Ignacio I.Chen, LiepingPeng, DiWang, ShanshanUllrich, Stephen E.Heymach, John V.Kurie, Jonathan M.Qin, F. Xiao-Feng
Ewha Authors
안영호
SCOPUS Author ID
안영호scopus
Issue Date
2014
Journal Title
NATURE COMMUNICATIONS
ISSN
2041-1723JCR Link
Citation
vol. 5
Publisher
NATURE PUBLISHING GROUP
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
Immunosuppression of tumour-infiltrating lymphocytes (TIL) is a common feature of advanced cancer, but its biological basis has remained obscure. We demonstrate here a molecular link between epithelial-to-mesenchymal transition (EMT) and CD8(+) TIL immunosuppression, two key drivers of cancer progression. We show that microRNA-200 (miR-200), a cell-autonomous suppressor of EMT and metastasis, targets PD-L1. Moreover, ZEB1, an EMTactivator and transcriptional repressor of miR-200, relieves miR-200 repression of PD-L1 on tumour cells, leading to CD8(+) T-cell immunosuppression and metastasis. These findings are supported by robust correlations between the EMT score, miR-200 levels and PD-L1 expression in multiple human lung cancer datasets. In addition to revealing a link between EMT and T-cell dysfunction, these findings also show that ZEB1 promotes metastasis through a heretofore unappreciated cell non-autonomous mechanism, and suggest that subgroups of patients in whom malignant progression is driven by EMT activators may respond to treatment with PD-L1 antagonists.
DOI
10.1038/ncomms6241
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의학전문대학원 > 의학과 > Journal papers
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