Your browser doesn't support javascript.
loading
Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade.
Ishizuka, Jeffrey J; Manguso, Robert T; Cheruiyot, Collins K; Bi, Kevin; Panda, Arpit; Iracheta-Vellve, Arvin; Miller, Brian C; Du, Peter P; Yates, Kathleen B; Dubrot, Juan; Buchumenski, Ilana; Comstock, Dawn E; Brown, Flavian D; Ayer, Austin; Kohnle, Ian C; Pope, Hans W; Zimmer, Margaret D; Sen, Debattama R; Lane-Reticker, Sarah K; Robitschek, Emily J; Griffin, Gabriel K; Collins, Natalie B; Long, Adrienne H; Doench, John G; Kozono, David; Levanon, Erez Y; Haining, W Nicholas.
Afiliación
  • Ishizuka JJ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Manguso RT; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Cheruiyot CK; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Bi K; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Panda A; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Iracheta-Vellve A; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Miller BC; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Du PP; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Yates KB; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Dubrot J; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Buchumenski I; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Comstock DE; Division of Medical Sciences, Harvard Medical School, Boston, MA, USA.
  • Brown FD; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Ayer A; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Kohnle IC; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Pope HW; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Zimmer MD; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Sen DR; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Lane-Reticker SK; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Robitschek EJ; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Griffin GK; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Collins NB; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Long AH; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Doench JG; Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
  • Kozono D; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Levanon EY; Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Haining WN; Division of Medical Sciences, Harvard Medical School, Boston, MA, USA.
Nature ; 565(7737): 43-48, 2019 01.
Article en En | MEDLINE | ID: mdl-30559380
ABSTRACT
Most patients with cancer either do not respond to immune checkpoint blockade or develop resistance to it, often because of acquired mutations that impair antigen presentation. Here we show that loss of function of the RNA-editing enzyme ADAR1 in tumour cells profoundly sensitizes tumours to immunotherapy and overcomes resistance to checkpoint blockade. In the absence of ADAR1, A-to-I editing of interferon-inducible RNA species is reduced, leading to double-stranded RNA ligand sensing by PKR and MDA5; this results in growth inhibition and tumour inflammation, respectively. Loss of ADAR1 overcomes resistance to PD-1 checkpoint blockade caused by inactivation of antigen presentation by tumour cells. Thus, effective anti-tumour immunity is constrained by inhibitory checkpoints such as ADAR1 that limit the sensing of innate ligands. The induction of sufficient inflammation in tumours that are sensitized to interferon can bypass the therapeutic requirement for CD8+ T cell recognition of cancer cells and may provide a general strategy to overcome immunotherapy resistance.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_malignant_skin_melanoma Asunto principal: Melanoma Experimental / Adenosina Desaminasa / Proteínas de Unión al ARN / Resistencia a Antineoplásicos / Receptor de Muerte Celular Programada 1 / Puntos de Control del Ciclo Celular Límite: Animals Idioma: En Revista: Nature Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_malignant_skin_melanoma Asunto principal: Melanoma Experimental / Adenosina Desaminasa / Proteínas de Unión al ARN / Resistencia a Antineoplásicos / Receptor de Muerte Celular Programada 1 / Puntos de Control del Ciclo Celular Límite: Animals Idioma: En Revista: Nature Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos