You are here

Nat Biotechnol DOI:10.1038/s41587-021-01021-3

Unannotated proteins expand the MHC-I-restricted immunopeptidome in cancer.

Publication TypeJournal Article
Year of Publication2022
AuthorsOuspenskaia, T, Law, T, Clauser, KR, Klaeger, S, Sarkizova, S, Aguet, F, Li, B, Christian, E, Knisbacher, BA, Le, PM, Hartigan, CR, Keshishian, H, Apffel, A, Oliveira, G, Zhang, W, Chen, S, Chow, YTing, Ji, Z, Jungreis, I, Shukla, SA, Justesen, S, Bachireddy, P, Kellis, M, Getz, G, Hacohen, N, Keskin, DB, Carr, SA, Wu, CJ, Regev, A
JournalNat Biotechnol
Volume40
Issue2
Pages209-217
Date Published2022 Feb
ISSN1546-1696
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.

DOI10.1038/s41587-021-01021-3
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/34663921?dopt=Abstract

Alternate JournalNat Biotechnol
PubMed ID34663921
Grant ListU24-CA210986 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
R01 HG004037 / HG / NHGRI NIH HHS / United States
T32HG002295 / / U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) /
SPORE-2P50CA101942-11A1 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
U24CA210979 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
T32CA207021 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
U41HG007234 / / U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) /
R21 CA216772-01A1 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
U41 HG007234 / HG / NHGRI NIH HHS / United States
R50 CA211482 / CA / NCI NIH HHS / United States
ALTF 14-2018 / / European Molecular Biology Organization (EMBO) /
R50CA211482 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /
5R01HL103532 / / U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
U01 CA214125 / CA / NCI NIH HHS / United States
R01 HG004037 / HG / NHGRI NIH HHS / United States
U01 CA214125 / CA / NCI NIH HHS / United States