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Unannotated proteins expand the MHC-I-restricted immunopeptidome in cancer.
Ouspenskaia, Tamara; Law, Travis; Clauser, Karl R; Klaeger, Susan; Sarkizova, Siranush; Aguet, François; Li, Bo; Christian, Elena; Knisbacher, Binyamin A; Le, Phuong M; Hartigan, Christina R; Keshishian, Hasmik; Apffel, Annie; Oliveira, Giacomo; Zhang, Wandi; Chen, Sarah; Chow, Yuen Ting; Ji, Zhe; Jungreis, Irwin; Shukla, Sachet A; Justesen, Sune; Bachireddy, Pavan; Kellis, Manolis; Getz, Gad; Hacohen, Nir; Keskin, Derin B; Carr, Steven A; Wu, Catherine J; Regev, Aviv.
Afiliação
  • Ouspenskaia T; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Law T; Flagship Labs 69, Cambridge, MA, USA.
  • Clauser KR; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Klaeger S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Sarkizova S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Aguet F; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Li B; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
  • Christian E; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Knisbacher BA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Le PM; Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Hartigan CR; Harvard University, Cambridge, MA, USA.
  • Keshishian H; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Apffel A; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Oliveira G; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Zhang W; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chen S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chow YT; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Ji Z; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Jungreis I; Phillips Academy, Andover, MA, USA.
  • Shukla SA; Harvard University, Cambridge, MA, USA.
  • Justesen S; Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Bachireddy P; Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA.
  • Kellis M; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Getz G; MIT Computer Science and Artificial Intelligence Laboratory, Cambridge, MA, USA.
  • Hacohen N; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Keskin DB; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Carr SA; Immunitrack, Copenhagen, Denmark.
  • Wu CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Regev A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nat Biotechnol ; 40(2): 209-217, 2022 02.
Article em En | MEDLINE | ID: mdl-34663921
ABSTRACT
Tumor-associated epitopes presented on MHC-I that can activate the immune system against cancer cells are typically identified from annotated protein-coding regions of the genome, but whether peptides originating from novel or unannotated open reading frames (nuORFs) can contribute to antitumor immune responses remains unclear. Here we show that peptides originating from nuORFs detected by ribosome profiling of malignant and healthy samples can be displayed on MHC-I of cancer cells, acting as additional sources of cancer antigens. We constructed a high-confidence database of translated nuORFs across tissues (nuORFdb) and used it to detect 3,555 translated nuORFs from MHC-I immunopeptidome mass spectrometry analysis, including peptides that result from somatic mutations in nuORFs of cancer samples as well as tumor-specific nuORFs translated in melanoma, chronic lymphocytic leukemia and glioblastoma. NuORFs are an unexplored pool of MHC-I-presented, tumor-specific peptides with potential as immunotherapy targets.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Imunoterapia / Melanoma 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: Imunoterapia / Melanoma Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article