title: MYC regulates the antitumor immune response through CD47 and PD-L1.
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.
authors.affiliation: Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Casey
authors.affiliation: Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Tong
authors.affiliation: Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Do
authors.affiliation: Comprehensive Cancer Center Mainfranken, Core Unit Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Walz
authors.affiliation: Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Kelly N
authors.initials: KN
authors.lastname: Fitzgerald
authors.affiliation: Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Arvin M
authors.initials: AM
authors.lastname: Gouw
authors.affiliation: Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Virginie
authors.initials: V
authors.lastname: Baylot
authors.affiliation: 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.
authors.forename: Ines
authors.initials: I
authors.lastname: Gütgemann
authors.affiliation: 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.
authors.forename: Martin
authors.initials: M
authors.lastname: Eilers
authors.affiliation: Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. dfelsher@stanford.edu.
authors.forename: Dean W
authors.initials: DW
authors.lastname: Felsher
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics*; D051928:CD47 Antigen / Q000235:genetics*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D019169:Jurkat Cells; D008223:Lymphoma / Q000235:genetics / Q000276:immunology; D051379:Mice; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D060890:B7-H1 Antigen; D051928:CD47 Antigen; C489427:MYC protein, human; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering