MYC 通过 CD47 和程序性死亡受体配体 1（PD-L1）调节抗肿瘤免疫反应。
MYC regulates the antitumor immune response through CD47 and PD-L1.
作者信息
Casey Stephanie C, Tong Ling, Li Yulin, Do Rachel, Walz Susanne, Fitzgerald Kelly N, Gouw Arvin M, Baylot Virginie, Gütgemann Ines, Eilers Martin, Felsher Dean W
机构信息
Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Comprehensive Cancer Center Mainfranken, Core Unit Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
出版信息
Science. 2016 Apr 8;352(6282):227-31. doi: 10.1126/science.aac9935. Epub 2016 Mar 10.
The MYC oncogene codes for a transcription factor that is overexpressed in many human cancers. Here we show that MYC regulates the expression of two immune checkpoint proteins on the tumor cell surface: the innate immune regulator CD47 (cluster of differentiation 47) and the adaptive immune checkpoint PD-L1 (programmed death-ligand 1). Suppression of MYC in mouse tumors and human tumor cells caused a reduction in the levels of CD47 and PD-L1 messenger RNA and protein. MYC was found to bind directly to the promoters of the Cd47 and Pd-l1 genes. MYC inactivation in mouse tumors down-regulated CD47 and PD-L1 expression and enhanced the antitumor immune response. In contrast, when MYC was inactivated in tumors with enforced expression of CD47 or PD-L1, the immune response was suppressed, and tumors continued to grow. Thus, MYC appears to initiate and maintain tumorigenesis, in part, through the modulation of immune regulatory molecules.
MYC癌基因编码一种在许多人类癌症中过度表达的转录因子。我们在此表明，MYC调节肿瘤细胞表面两种免疫检查点蛋白的表达：先天性免疫调节因子CD47（分化簇47）和适应性免疫检查点PD-L1（程序性死亡配体1）。在小鼠肿瘤和人类肿瘤细胞中抑制MYC会导致CD47和PD-L1信使核糖核酸及蛋白质水平降低。研究发现，MYC可直接结合Cd47和Pd-l1基因的启动子。小鼠肿瘤中的MYC失活下调了CD47和PD-L1的表达，并增强了抗肿瘤免疫反应。相反，当在强制表达CD47或PD-L1的肿瘤中使MYC失活时，免疫反应受到抑制，肿瘤继续生长。因此，MYC似乎部分地通过调节免疫调节分子来启动和维持肿瘤发生。
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