✨ We are thankful to the @CancerCell editorial team and the reviewers for their constructive comments, and I am grateful to have such a wonderful team. (7/7)

🏥 Patient data completed the picture: Primary melanoma tumors with low TYW2 showed enhanced responses to ICB, even in patients with low TMB (@Tiangen). Translation fidelity defects may help predict immunotherapy responders, opening new paths for precision cancer treatment. (6/7)

Together with Yaron Carmi, we identified FS peptides that triggered robust T cell responses. Moreover, these peptides elicited de novo T cell responses specifically in TYW2-KO tumor-bearing mice! (5/7)

🐭 In mice, TYW2 loss increased tumor immunogenicity, specifically in immunocompetent mice. scRNA-seq revealed that TYW2-KO tumors were enriched for exhausted T cells. Indeed, TYW2-KO tumor-bearing mice were sensitive to immune checkpoint blockade (ICB) therapy. (4/7)

Furthermore, in vitro T cell stimulation assays (@Johannaolweus & team) demonstrated that these aberrant peptides are potent immune triggers! Could translation errors fuel anti-tumor immunity? (3/7)

🧬 Loss of TYW2, a tRNA modifier, disrupts translation fidelity—causing ribosomes to pause at Phe codons and increasing frameshift (FS) events. This generates out-of-frame peptides, which are presented by MHC class I molecules. (2/7)

All this is thanks to the hard work and wonderful collaboration with Sapir Cohen Shvefel, Joy Pai, the Sathpathy lab, the Ruppin lab, Mitch Levesque, @yardenasamuels.bsky.social
and colleagues.
#CancerResearch #Immunotherapy #ITH