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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.
Afiliação
  • 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 em 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T / Neoplasias Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article