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
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.
Oncoimmunology. 2016 Sep 26;5(11):e1234570. doi: 10.1080/2162402X.2016.1234570. eCollection 2016.
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 Krasp53-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.
癌细胞调节炎性细胞的募集和功能，以创建有利于肿瘤生长和转移的免疫抑制微环境。然而，促进肿瘤内免疫抑制的肿瘤衍生调节程序仍不清楚。在此，我们在基于Krasp53的小鼠模型中表明，骨形态发生蛋白4（BMP4）增强肺癌细胞间充质亚群中T细胞共抑制受体配体PD-L1的表达，导致深刻的CD8 T细胞介导的免疫抑制，促进肿瘤生长和转移。我们之前在该模型中报道，BMP4作为一种促肿瘤发生因子，由miR-200通过GATA4/6调节。因此，BMP4介导的免疫抑制是肿瘤中更大的miR-200导向基因表达程序的一部分，该程序促进肿瘤进展，这可能对癌症治疗具有重要意义。
