期刊
NATURE BIOTECHNOLOGY
卷 40, 期 2, 页码 209-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41587-021-01021-3
关键词
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资金
- Klarman Cell Observatory
- HHMI
- NIH [NCI-1R01CA155010-02, NHLBI-5R01HL103532-03, NIH/NCI R21 CA216772-01A1, NCI-SPORE-2P50CA101942-11A1, NHGRI T32HG002295, NIH/NCI T32CA207021, NCI R50CA211482, NHGRI U41HG007234, R01 HG004037]
- NCI Clinical Proteomic Tumor Analysis Consortium grant [NIH/NCI U24-CA210986, NIH/NCI U01 CA214125, NIH/NCI U24CA210979]
- G. Harold and Leila Y. Mathers Foundation
- Koch Institute for Integrative Cancer Research at MIT
- Dana-Farber/Harvard Cancer Center
- Parker Institute for Cancer Immunotherapy
- long-term EMBO fellowship [ALTF 14-2018]
- Amy Strelzer Manasevit Grant
- American Society of Hematology Scholar Award
- American-Italian Cancer Foundation
Peptides originating from novel or unannotated open reading frames (nuORFs) detected by ribosome profiling can be displayed on MHC-I of cancer cells, serving as additional sources of cancer antigens. These nuORFs represent an unexplored pool of tumor-specific peptides with potential as immunotherapy targets.
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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