| Literature DB >> 34663921 |
Tamara Ouspenskaia1,2, Travis Law1, Karl R Clauser1, Susan Klaeger1, Siranush Sarkizova1,3, François Aguet1, Bo Li4,5, Elena Christian6, Binyamin A Knisbacher1, Phuong M Le7, Christina R Hartigan1, Hasmik Keshishian1, Annie Apffel1, Giacomo Oliveira7, Wandi Zhang7, Sarah Chen8, Yuen Ting Chow6, Zhe Ji9,10, Irwin Jungreis1,11, Sachet A Shukla1,7, Sune Justesen12, Pavan Bachireddy7, Manolis Kellis1,11, Gad Getz1, Nir Hacohen1,13, Derin B Keskin1,7,14,15,16, Steven A Carr1, Catherine J Wu17,18,19,20, Aviv Regev21,22,23.
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.Entities:
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Year: 2021 PMID： 34663921 DOI： 10.1038/s41587-021-01021-3
Source DB: PubMed Journal: Nat Biotechnol ISSN： 1087-0156 Impact factor: 54.908