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Science. 2016 Apr 8;352(6282):227-31. doi: 10.1126/science.aac9935. Epub 2016 Mar 10.

MYC regulates the antitumor immune response through CD47 and PD-L1.

Author information

1
Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2
Comprehensive Cancer Center Mainfranken, Core Unit Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
3
Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany.
4
Comprehensive Cancer Center Mainfranken, Core Unit Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany. Theodor Boveri Institute, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
5
Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. dfelsher@stanford.edu.

Abstract

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.

PMID:
26966191
PMCID:
PMC4940030
DOI:
10.1126/science.aac9935
[Indexed for MEDLINE]
Free PMC Article

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