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

Limo Chen, Xiaohui Yi, Sangeeta Goswami, Young Ho Ahn, Jonathon D. Roybal, Yongbin Yang, Lixia Diao, Di Peng, David Peng, Jared J. Fradette, Jing Wang, Lauren A. Byers, Jonathan M. Kurie, Stephen E. Ullrich, F. Xiao Feng Qin, Don L. Gibbons

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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 KrasLA1/+p53R172HΔg/+-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.

Original languageEnglish
Article numbere1234570
JournalOncoImmunology
Volume5
Issue number11
DOIs
StatePublished - 1 Nov 2016

Keywords

  • BMP4
  • EMT
  • immunotherapy
  • lung cancer
  • miR-200
  • PD-L1

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