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

Jul 10, 2024 | Magazine: Science Advances

Marta E Camarena 1, Patrick Theunissen 2, Marta Ruiz 2, Jorge Ruiz-Orera 3, Beatriz Calvo-Serra 4, Robert Castelo 4, Carla Castro 2, Pablo Sarobe 2 5 6 7, Puri Fortes 2 5 6 7 8, Júlia Perera-Bel 1, M Mar Albà 1 9

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.

CITATION Sci Adv. 2024 Jul 12;10(28):eadn3628. doi: 10.1126/sciadv.adn3628. Epub 2024 Jul 10.

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