Growth and metastasis of lung adenocarcinoma is potentiated by BMP4-mediated immunosuppression
- 주제(키워드) BMP4 , EMT , immunotherapy , lung cancer , miR-200 , PD-L1
- 등재 SCIE, SCOPUS
- 발행기관 TAYLOR & FRANCIS INC
- 발행년도 2016
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000139710
- 본문언어 영어
- Published As http://dx.doi.org/10.1080/2162402X.2016.1234570
초록/요약
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(R172H Delta g/+)-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.
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