The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Unannotated proteins expand the MHC-I-restricted immunopeptidome in cancer
Open accessAbstract
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. New tumor epitopes are discovered by ribosome profiling and immunopeptidome mass spectrometry.
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Cites
1 retracted
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Cited by
TCR-engineered T cell therapy in solid tumors: State of the art and perspectives
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Metadata
- Authors
- Ouspenskaia, T., Law, T., Clauser, K. R., Klaeger, S., Sarkizova, S., Aguet, F., Li, B., Christian, E., Knisbacher, B. A., Le, P. M., Hartigan, C. R., Keshishian, H., Apffel, A., Oliveira, G., Zhang, W., Chen, S., Chow, Y. T., Ji, Z., Jungreis, I., Shukla, S. A., Justesen, S., Bachireddy, P., Kellis, M., Getz, G., Hacohen, N., Keskin, D. B., Carr, S. A., Wu, C. J., & Regev, A.
- Venue
- Nature Biotechnology
- Published
- 2021-10-18
- Volume
- 40
- Issue
- 2
- Pages
- 209-217
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W3205324211
- Cited by
- 298
- References
- 55
- FWCI
- 12.68
- Type
- journal article
- Language
- en
- Open access
- green
- Licence
- www.springer.com/tdm (tdm)
- www.springer.com/tdm (vor)
- Funders
- Leukemia and Lymphoma Society
- Cancer Research Institute
- U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (T32HG002295, U41HG007234, R01 HG004037)
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (T32CA207021, R50CA211482, U24CA210979, R21 CA216772-01A1, SPORE-2P50CA101942-11A1, U24-CA210986, U01 CA214125)
- European Molecular Biology Organization (ALTF 14-2018)
- American-Italian Cancer Foundation
- American Society of Hematology
- Amy Strelzer Manasevit Grant
- U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (5R01HL103532)
- Howard Hughes Medical Institute
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- Ouspenskaia, T., Law, T., Clauser, K. R., Klaeger, S., Sarkizova, S., Aguet, F., Li, B., Christian, E., Knisbacher, B. A., Le, P. M., Hartigan, C. R., Keshishian, H., Apffel, A., Oliveira, G., Zhang, W., Chen, S., Chow, Y. T., Ji, Z., Jungreis, I., . . . Regev, A. (2022). Unannotated proteins expand the MHC-I-restricted immunopeptidome in cancer. Nature Biotechnology. https://doi.org/10.1038/s41587-021-01021-3
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