Upstream open reading frames (uORFs) represent translational control elements within eukaryotic transcript leader sequences. Recent data showed that uORFs can encode for biologically active proteins and human leucocyte antigen (HLA)-presented peptides and suggest their potential role in cancer cell development and survival. However, it is so far unclear if uORF-encoded peptides could serve as tumor-associated antigen targets and thus also play a role in cancer immune surveillance. Combining mass spectrometry-based immunopeptidome analysis in primary tumor and healthy tissues and evaluation of proto-oncogene-associated uORF-mediated translational control we here identified a panel of HLA-presented tumor-associated uORF-derived antigens. These uORF-derived tumor antigens were further shown to induce multifunctional antigen-specific T cells, validating their suitability as antigen targets for T cell-based cancer immunotherapy. Our data further unravel the role of uORF-encoded peptides in malignant disease, suggesting uORF-derived tumor-associated antigens as targets for anti-cancer immune surveillance and immunotherapy development.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Cancer ; Uorf ; Immunotherapy ; Immunopeptidomics ; Hla peptides ; DatasetType:Proteomics
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Principal Investigators: (in alphabetical order) |
Juliane S. Walz, Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital T�bingen, T�bingen, Germany, N/A |
| Submitting User: | ccms |
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