Microproteins encoded by noncanonical ORFs are a major source of tumor-specific antigens in a liver cancer patient meta-cohort

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  • dc.contributor.author Camarena, Marta E.
  • dc.contributor.author Theunissen, Patrick
  • dc.contributor.author Ruiz, Marta
  • dc.contributor.author Ruiz Orera, Jorge, 1988-
  • dc.contributor.author Calvo Serra, Beatriz
  • dc.contributor.author Castelo Valdueza, Robert
  • dc.contributor.author Castro Alejos, Carla
  • dc.contributor.author Sarobe, Pablo
  • dc.contributor.author Fortes, Puri
  • dc.contributor.author Perera Bel, Júlia
  • dc.contributor.author Albà Soler, Mar
  • dc.date.accessioned 2024-09-18T06:26:10Z
  • dc.date.available 2024-09-18T06:26:10Z
  • dc.date.issued 2024
  • dc.description.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.
  • dc.description.sponsorship This work was supported by the following grants and agencies: research projects PID2019-105595GB, PID2021-122726NB-I00, and PID2021-128791OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF: A way of making Europe” by the “European Union”; PI19/00004, PI20/00260, and PI22/00171, funded by Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union and FEDER; 0011-1383-2019-000006 and 0011-1411-2021-000070, funded by Gobierno de Navarra; RTI2018-101759-B-I00 and the Instituto de Salud Carlos III, which finances Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREhd) and Red Española de Terapias Avanzadas TERAV ISCIII [RICORS: (RD21/0017), financed by the EU (NextGenerationEU, Plan de Recuperación Transformación y Resiliencia)]; AECC IDEAS20169FORT by Scientific Foundation of the Spanish Association Against Cancer; 2021SGR00042 by Generalitat de Catalunya; Ayudas Fundación BBVA a Proyectos de Investigación Científica en Biomedicina 2021; and European Reseach Council Advanced Grant NovoGenePop 101052538. Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Camarena 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.adn3628
  • dc.identifier.doi http://dx.doi.org/10.1126/sciadv.adn3628
  • dc.identifier.issn 2375-2548
  • dc.identifier.uri http://hdl.handle.net/10230/61136
  • dc.language.iso eng
  • dc.publisher American Association for the Advancement of Science (AAAS)
  • dc.relation.ispartof Sci Adv. 2024 Jul 12;10(28):eadn3628
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101052538
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-105595GB
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-122726NB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PID2021-128791OB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-101759-B-I00
  • dc.rights Copyright © 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.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Fetge--Càncer
  • dc.title Microproteins encoded by noncanonical ORFs are a major source of tumor-specific antigens in a liver cancer patient meta-cohort
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

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