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Cited by 966

The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.

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

Open access
Chen, Limo, Gibbons, Don L., Goswami, Sangeeta, Cortez, Maria Angelica, Ahn, Young-Ho, Byers, Lauren A., Zhang, Xuejun, Yi, Xiaohui, Dwyer, David, Lin, Wei, Diao, Lixia, Wang, Jing, Roybal, Jonathon D., Patel, Mayuri, Ungewiss, Christin, Peng, David, Antonia, Scott, Mediavilla-Varela, Melanie, Robertson, Gordon, Jones, Steve, Suraokar, Milind, Welsh, James W., Erez, Baruch, Wistuba, Ignacio I., Chen, Lieping, Peng, Di, Wang, Shanshan, Ullrich, Stephen E., Heymach, John V., Kurie, Jonathan M., Qin, F. Xiao-Feng·2014·Nature Communications
DOI 10.1038/ncomms6241
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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 EMT activator 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. Tumour-infiltrating lymphocytes (TILs) can be suppressed by the tumour, but how this occurs is not clear. Here the authors show that the miR-200 family, which suppresses epithelial–mesenchymal transition, also targets tumour cell PD-L1 and thereby intratumoral immunosuppression and metastasis.

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Metadata

Authors
Chen, L., Gibbons, D. L., Goswami, S., Cortez, M. A., Ahn, Y.-H., Byers, L. A., Zhang, X., Yi, X., Dwyer, D., Lin, W., Diao, L., Wang, J., Roybal, J. D., Patel, M., Ungewiss, C., Peng, D., Antonia, S., Mediavilla-Varela, M., Robertson, G., Jones, S., Suraokar, M., Welsh, J. W., Erez, B., Wistuba, I. I., Chen, L., Peng, D., Wang, S., Ullrich, S. E., Heymach, J. V., Kurie, J. M., & Qin, F. X.-F.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2014-10-28
Volume
5
Issue
1
Pages
5241-5241
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms6241
OpenAlex
W1996863944
Cited by
966
References
15
FWCI
22.40
Type
journal article
Language
en
Open access
bronze

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