Proud of @yardenasamuels.bsky.social for her fascinating plenary session at the @theaacr.bsky.social annual meeting in Chicago! A great thank you to the program committee chairs, Drs. Matthew Vander Heiden and Lillian Siu for this opportunity. @mvhlab.bsky.social @lilliansiu.bsky.social #AACR25

In a study published in @cp-cancercell.bsky.social researchers from our lab manipulated cancer cells into making themselves visible to the immune system, creating a new approach that gives hope to patients with previously untreatable disease>> bit.ly/cancer-expos...

🏥 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)

Thrilled to share our latest work in Cancer Cell! 🚨 Led by Chen Weller, Osnat Bartok, with amazing collaborators Chris Mcginnis, Ansuman Satpathy, Andreas Schlosser, Eytan Ruppin & more, we reveal that impaired translation fidelity enhances anti-tumor immunity!🧵(1/7)