title: Growth and metastasis of lung adenocarcinoma is potentiated by BMP4-mediated immunosuppression.
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.
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Limo
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Goswami
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Molecular Medicine and Tissue Injury Defense Research Center, Ewha Womans University School of Medicine, Yangcheon-gu, Seoul, Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Ahn
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Jonathon D
authors.initials: JD
authors.lastname: Roybal
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai, China.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Lixia
authors.initials: L
authors.lastname: Diao
authors.affiliation: Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China.
authors.forename: Di
authors.initials: D
authors.lastname: Peng
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: David
authors.initials: D
authors.lastname: Peng
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Fradette
authors.affiliation: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Byers
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Kurie
authors.affiliation: Department of Immunology, The University of Texas MD Anderson Cancer Center , Houston, TX, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Ullrich
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, China.
authors.forename: F Xiao-Feng
authors.initials: FX
authors.lastname: Qin
authors.affiliation: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Don L
authors.initials: DL
authors.lastname: Gibbons
keywords: BMP4; EMT; PD-L1; immunotherapy; lung cancer; miR-200