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Genome-wide Screens Identify Lineage- and Tumor-Specific Genes Modulating MHC-I- and MHC-II-Restricted Immunosurveillance of Human Lymphomas.
Dersh, Devin; Phelan, James D; Gumina, Megan E; Wang, Boya; Arbuckle, Jesse H; Holly, Jaroslav; Kishton, Rigel J; Markowitz, Tovah E; Seedhom, Mina O; Fridlyand, Nathan; Wright, George W; Huang, Da Wei; Ceribelli, Michele; Thomas, Craig J; Lack, Justin B; Restifo, Nicholas P; Kristie, Thomas M; Staudt, Louis M; Yewdell, Jonathan W.
  • Dersh D; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: devin.dersh@nih.gov.
  • Phelan JD; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gumina ME; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wang B; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Arbuckle JH; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Holly J; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Kishton RJ; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 USA.
  • Markowitz TE; NIAID Collaborative Bioinformatics Resource, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
  • Seedhom MO; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Fridlyand N; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wright GW; Biometric Research Branch, Division of Cancer Diagnosis and Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Huang DW; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ceribelli M; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
  • Thomas CJ; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.
  • Lack JB; NIAID Collaborative Bioinformatics Resource, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
  • Restifo NP; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 USA.
  • Kristie TM; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Staudt LM; Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Yewdell JW; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jyewdell@niaid.nih.gov.
Immunity ; 54(1): 116-131.e10, 2021 01 12.
Article en En | MEDLINE | ID: mdl-33271120
ABSTRACT
Tumors frequently subvert major histocompatibility complex class I (MHC-I) peptide presentation to evade CD8+ T cell immunosurveillance, though how this is accomplished is not always well defined. To identify the global regulatory networks controlling antigen presentation, we employed genome-wide screening in human diffuse large B cell lymphomas (DLBCLs). This approach revealed dozens of genes that positively and negatively modulate MHC-I cell surface expression. Validated genes clustered in multiple pathways including cytokine signaling, mRNA processing, endosomal trafficking, and protein metabolism. Genes can exhibit lymphoma subtype- or tumor-specific MHC-I regulation, and a majority of primary DLBCL tumors displayed genetic alterations in multiple regulators. We established SUGT1 as a major positive regulator of both MHC-I and MHC-II cell surface expression. Further, pharmacological inhibition of two negative regulators of antigen presentation, EZH2 and thymidylate synthase, enhanced DLBCL MHC-I presentation. These and other genes represent potential targets for manipulating MHC-I immunosurveillance in cancers, infectious diseases, and autoimmunity.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos B / Antígenos de Histocompatibilidad Clase I / Biomarcadores de Tumor / Antígenos de Histocompatibilidad Clase II / Linfoma de Células B Grandes Difuso / Antígenos HLA Límite: Humans Idioma: En Año: 2021 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos B / Antígenos de Histocompatibilidad Clase I / Biomarcadores de Tumor / Antígenos de Histocompatibilidad Clase II / Linfoma de Células B Grandes Difuso / Antígenos HLA Límite: Humans Idioma: En Año: 2021 Tipo del documento: Article