Your browser doesn't support javascript.
loading
Cancer genes disfavoring T cell immunity identified via integrated systems approach.
Kishton, Rigel J; Patel, Shashank J; Decker, Amy E; Vodnala, Suman K; Cam, Maggie; Yamamoto, Tori N; Patel, Yogin; Sukumar, Madhusudhanan; Yu, Zhiya; Ji, Michelle; Henning, Amanda N; Gurusamy, Devikala; Palmer, Douglas C; Stefanescu, Roxana A; Girvin, Andrew T; Lo, Winifred; Pasetto, Anna; Malekzadeh, Parisa; Deniger, Drew C; Wood, Kris C; Sanjana, Neville E; Restifo, Nicholas P.
Afiliación
  • Kishton RJ; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: kishtonr@gmail.com.
  • Patel SJ; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA.
  • Decker AE; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Vodnala SK; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA.
  • Cam M; CCR Collaborative Bioinformatics Resource (CCBR), Office of Science and Technology Resources, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Yamamoto TN; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA; Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Patel Y; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA.
  • Sukumar M; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA.
  • Yu Z; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA.
  • Ji M; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA.
  • Henning AN; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA.
  • Gurusamy D; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA.
  • Palmer DC; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA.
  • Stefanescu RA; Palantir Technologies, Washington, DC 20007, USA.
  • Girvin AT; Palantir Technologies, Washington, DC 20007, USA.
  • Lo W; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Pasetto A; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Malekzadeh P; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Deniger DC; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
  • Wood KC; Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Sanjana NE; New York Genome Center, New York, NY 10013, USA; Department of Biology, New York University, New York, NY 10003, USA.
  • Restifo NP; Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Center for Cell-Based Therapy, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: drnickrestifo@gmail.com.
Cell Rep ; 40(5): 111153, 2022 08 02.
Article en En | MEDLINE | ID: mdl-35926468
ABSTRACT
Adoptive T cell therapies (ACT) have been curative for a limited number of cancer patients. The sensitization of cancer cells to T cell killing may expand the benefit of these therapies for more patients. To this end, we use a three-step approach to identify cancer genes that disfavor T cell immunity. First, we profile gene transcripts upregulated by cancer under selection pressure from T cell killing. Second, we identify potential tumor gene targets and pathways that disfavor T cell killing using signaling pathway activation libraries and genome-wide loss-of-function CRISPR-Cas9 screens. Finally, we implement pharmacological perturbation screens to validate these targets and identify BIRC2, ITGAV, DNPEP, BCL2, and ERRα as potential ACT-drug combination candidates. Here, we establish that BIRC2 limits antigen presentation and T cell recognition of tumor cells by suppressing IRF1 activity and provide evidence that BIRC2 inhibition in combination with ACT is an effective strategy to increase efficacy.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfocitos T / Neoplasias Límite: Humans Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Linfocitos T / Neoplasias Límite: Humans Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article