Growth and metastasis of lung adenocarcinoma is potentiated by BMP4-mediated immunosuppression. (1st November 2016)

• Record Type: Journal Article
• Authors: Chen, Limo; Yi, Xiaohui; Goswami, Sangeeta; Ahn, Young-Ho; Roybal, Jonathon D.; Yang, Yongbin; Diao, Lixia; Peng, Di; Peng, David; Fradette, Jared J.; Wang, Jing; Byers, Lauren A.; Kurie, Jonathan M.; Ullrich, Stephen E.; Qin, F. Xiao-Feng; Gibbons, Don L.
• Is Part Of: Oncoimmunology. Volume 5:Number 11(2016)
• Publication Date: 2016-11-01
• Subjects: BMP4 -- EMT -- immunotherapy -- lung cancer -- miR-200 -- PD-L1; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2016.1234570
• Languages: English
• ISSNs: 2162-402X

Abstract

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.