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

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 checkpoi...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2016-04, Vol.352 (6282), p.227-231
Main Authors: 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.
Format: Article
Language:English
Subjects:
Animals
B7-H1 Antigen - genetics
Cancer
CD47 Antigen - genetics
Cell Line, Tumor
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - immunology
Down-Regulation
Gene expression
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Humans
Immune Tolerance - genetics
Immunotherapy
Individualized Instruction
Jurkat Cells
Lymphoma - genetics
Lymphoma - immunology
Mice
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - immunology
Promoter Regions, Genetic
Proteins
Proto-Oncogene Proteins c-myc - genetics
Proto-Oncogene Proteins c-myc - metabolism
RNA, Small Interfering - genetics
Tumors
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aac9935