Weller, Chen and Bartok, Osnat and Mcginnis, Christopher S. and Palashati, Heyilimu and Chang, Tian-Gen and Malko, Dmitry and Shmueli, Merav D. and Nagao, Asuteka and Hayoun, Deborah and Murayama, Ayaka and Sakaguchi, Yuriko and Poulis, Panagiotis and Khatib, Aseel and Avigdor, Bracha Erlanger and Gordon, Sagi and Shvefel, Sapir Cohen and Zemanek, Marie J. and Nielsen, Morten M. and Boura-Halfon, Sigalit and Sagie, Shira and Gumpert, Nofar and Yang, Weiwen and Alexeev, Dmitry and Kyriakidou, Pelgia and Yao, Winnie and Zerbib, Mirie and Greenberg, Polina and Benedek, Gil and Litchfield, Kevin and Petrovich-Kopitman, Ekaterina and Nagler, Adi and Oren, Roni and Ben-Dor, Shifra and Levin, Yishai and Pilpel, Yitzhak and Rodnina, Marina and Cox, Jurgen and Merbl, Yifat and Satpathy, Ansuman T. and Carmi, Yaron and Erhard, Florian and Suzuki, Tsutomu and Buskirk, Allen R. and Olweus, Johanna and Ruppin, Eytan and Schlosser, Andreas and Samuels, Yardena (2025) Translation dysregulation in cancer as a source for targetable antigens. CANCER CELL, 43 (5). ISSN 1535-6108, 1878-3686
Full text not available from this repository. (Request a copy)Abstract
Aberrant peptides presented by major histocompatibility complex (MHC) molecules are targets for tumor eradication, as these peptides can be recognized as foreign by T cells. Protein synthesis in malignant cells is dysregulated, which may result in the generation and presentation of aberrant peptides that can be exploited for T cell-based therapies. To investigate the role of translational dysregulation in immunological tumor control, we disrupt translation fidelity by deleting tRNA wybutosine (yW)-synthesizing protein 2 (TYW2) in tumor cells and characterize the downstream impact on translation fidelity and immunogenicity using immunopeptidomics, genomics, and functional assays. These analyses reveal that TYW2 knockout (KO) cells generate immunogenic out-of-frame peptides. Furthermore, Tyw2 loss increases tumor immunogenicity and leads to anti-programmed cell death 1 (PD-1) checkpoint blockade sensitivity in vivo. Importantly, reduced TYW2 expression is associated with increased response to checkpoint blockade in patients. Together, we demonstrate that defects in translation fidelity drive tumor immunogenicity and may be leveraged for cancer immunotherapy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSFER-RNA; PEPTIDE IDENTIFICATION; IN-VIVO; PROTEIN; IMMUNOTHERAPY; OVEREXPRESSION; BIOSYNTHESIS; POSITION-37; BIOGENESIS; SEQUENCES; |
| Subjects: | 000 Computer science, information & general works > 004 Computer science 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Informatics and Data Science > Department Computational Life Science > Chair of Computational Immunology (Prof. Dr. Florian Erhard) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Mar 2026 14:32 |
| Last Modified: | 25 Mar 2026 14:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/68009 |
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