AI Article Synopsis
- Researchers have found that microproteins from noncanonical open reading frames (ncORFs) can produce tumor-specific antigens during cancer progression, potentially triggering immune responses.
- By analyzing RNA sequencing and other data from 117 liver cancer (hepatocellular carcinoma) tumors, they discovered that about 40% of these antigens likely come from ncORFs, including some that can initiate an immune response in humanized mice.
- The study also identified 33 long noncoding RNAs that express shared cancer antigens found in over 10% of the samples, suggesting new possibilities for developing cancer vaccines.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11235171 | PMC |
| http://dx.doi.org/10.1126/sciadv.adn3628 | DOI Listing |
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