Journal
SCIENCE
Volume 352, Issue 6282, Pages 227-231Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aac9935
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Funding
- NIH R01 [CA 089305, CA 170378, CA 184384, U01 CA 188383, U01 CA 114747]
- Cancer Research Institute Clinic and Laboratory Innovation Program
- NIH [1F32CA177139, 5T32AI07290]
- Alex's Lemonade Stand Foundation
- Deutsche Forschungsgemeinschaft (DFG) [Ei222/12-1]
- Deutsche Krebshilfe via the Comprehensive Cancer Center Mainfranken
- DFG [GU 1046/2-1]
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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.
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