Growth and metastasis of lung adenocarcinoma is potentiated by BMP4-mediated immunosuppression.

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Growth and metastasis of lung adenocarcinoma is potentiated by BMP4-mediated immunosuppression.

Oncoimmunology. 2016;5(11):e1234570

Authors: Chen L, Yi X, Goswami S, Ahn YH, Roybal JD, Yang Y, Diao L, Peng D, Peng D, Fradette JJ, Wang J, Byers LA, Kurie JM, Ullrich SE, Qin FX, Gibbons DL

Abstract
Cancer cells modulate the recruitment and function of inflammatory cells to create an immunosuppressive microenvironment that favors tumor growth and metastasis. However, the tumor-derived regulatory programs that promote intratumoral immunosuppression remain poorly defined. Here, we show in a Kras(LA1/+)p53(R172HΔg/+)-based mouse model that bone morphogenetic protein-4 (BMP4) augments the expression of the T cell co-inhibitory receptor ligand PD-L1 in the mesenchymal subset of lung cancer cells, leading to profound CD8(+) T cell-mediated immunosuppression, producing tumor growth and metastasis. We previously reported in this model that BMP4 functions as a pro-tumorigenic factor regulated by miR-200 via GATA4/6. Thus, BMP4-mediated immunosuppression is part of a larger miR-200-directed gene expression program in tumors that promotes tumor progression, which could have important implications for cancer treatment.

PMID: 27999749 [PubMed]

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