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| Item Type: | Article |
|---|---|
| Title: | Microproteins encoded by noncanonical ORFs are a major source of tumor-specific antigens in a liver cancer patient meta-cohort |
| Creators: |
Camarena, M.E.  ORCID: https://orcid.org/0000-0001-9319-6388, Theunissen, P. ORCID: https://orcid.org/0000-0002-6009-3574, Ruiz, M., Ruiz-Orera, J. ORCID: https://orcid.org/0000-0002-8317-0034, Calvo-Serra, B. ORCID: https://orcid.org/0000-0002-7614-396X, Castelo, R. ORCID: https://orcid.org/0000-0003-2229-4508, Castro, C. ORCID: https://orcid.org/0009-0006-6825-2329, Sarobe, P., Fortes, P. ORCID: https://orcid.org/0000-0001-7571-6220, Perera-Bel, J. ORCID: https://orcid.org/0000-0002-6809-132X and Albà, M.M.
|
| Abstract: | The expression of tumor-specific antigens during cancer progression can trigger an immune response against the tumor. Here, we investigate if microproteins encoded by noncanonical open reading frames (ncORFs) are a relevant source of tumor-specific antigens. We analyze RNA sequencing data from 117 hepatocellular carcinoma (HCC) tumors and matched healthy tissue together with ribosome profiling and immunopeptidomics data. Combining human leukocyte antigen-epitope binding predictions and experimental validation experiments, we conclude that around 40% of the tumor-specific antigens in HCC are likely to be derived from ncORFs, including two peptides that can trigger an immune response in humanized mice. We identify a subset of 33 tumor-specific long noncoding RNAs expressing novel cancer antigens shared by more than 10% of the HCC samples analyzed, which, when combined, cover a large proportion of the patients. The results of the study open avenues for extending the range of anticancer vaccines. |
| Keywords: | Neoplasm Antigens, Hepatocellular Carcinoma, Cohort Studies, Neoplastic Gene Expression Regulation, Liver Neoplasms, Micropeptides, Open Reading Frames, Long Noncoding RNA, Animals, Mice |
| Source: | Science Advances |
| ISSN: | 2375-2548 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 10 |
| Number: | 28 |
| Page Range: | eadn3628 |
| Date: | July 2024 |
| Official Publication: | https://doi.org/10.1126/sciadv.adn3628 |
| PubMed: | View item in PubMed |
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