Camarena, Marta E.Theunissen, PatrickRuiz, MartaRuiz Orera, Jorge, 1988-Calvo Serra, BeatrizCastelo Valdueza, RobertCastro Alejos, CarlaSarobe, PabloFortes, PuriPerera Bel, JúliaAlbà Soler, Mar2024-09-182024-09-182024Camarena ME, Theunissen P, Ruiz M, Ruiz-Orera J, Calvo-Serra B, Castelo R, et al. Microproteins encoded by noncanonical ORFs are a major source of tumor-specific antigens in a liver cancer patient meta-cohort. Sci Adv. 2024 Jul 12;10(28):eadn3628. DOI: 10.1126/sciadv.adn36282375-2548http://hdl.handle.net/10230/61136The 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.application/pdfengCopyright © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). This is an open-access article distributed under the terms of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Fetge--Càncerinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1126/sciadv.adn3628info:eu-repo/semantics/openAccess