Publication Date:
2016-03-12
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Casey, Stephanie C -- Tong, Ling -- Li, Yulin -- Do, Rachel -- Walz, Susanne -- Fitzgerald, Kelly N -- Gouw, Arvin M -- Baylot, Virginie -- Gutgemann, Ines -- Eilers, Martin -- Felsher, Dean W -- 1F32CA177139/CA/NCI NIH HHS/ -- 5T32AI07290/AI/NIAID NIH HHS/ -- CA 089305/CA/NCI NIH HHS/ -- CA 170378/CA/NCI NIH HHS/ -- CA 184384/CA/NCI NIH HHS/ -- U01 CA 114747/CA/NCI NIH HHS/ -- U01 CA 188383/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):227-31. doi: 10.1126/science.aac9935. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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 Wurzburg, Am Hubland, 97074 Wurzburg, Germany. ; 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. ; Comprehensive Cancer Center Mainfranken, Core Unit Bioinformatics, Biocenter, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany. Theodor Boveri Institute, Biocenter, University of Wurzburg, Am Hubland, 97074 Wurzburg, Germany. ; Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. dfelsher@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26966191" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD274/*genetics
;
Antigens, CD47/*genetics
;
Cell Line, Tumor
;
Cell Transformation, Neoplastic/genetics/*immunology
;
Down-Regulation
;
*Gene Expression Regulation, Neoplastic
;
Gene Knockdown Techniques
;
Humans
;
Immune Tolerance/*genetics
;
Jurkat Cells
;
Lymphoma/genetics/immunology
;
Mice
;
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics/immunology
;
Promoter Regions, Genetic
;
Proto-Oncogene Proteins c-myc/genetics/*metabolism
;
RNA, Small Interfering/genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
