Samuels Lab

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

Translation dysregulation in cancer as a source for targetable antigens Weller et al. substantiate the role of translation dysregulation in mediating anti-tumor immunity by demonstrating that TYW2 loss in melanoma cells induces aberrant peptide MHC presentation, increasing both tumor immunogenicity and sensitivity to ICB therapy. TYW2 expression levels in patients with melanoma predict clinical outcomes, highlighting translation regulatory factors as immunotherapy targets.

Online Now: Translation dysregulation in cancer as a source for targetable antigens

Translation dysregulation may serve as a new source for identifying cancer-associated antigens, and may also help to predict responses to checkpoint blockade bit.ly/3E4OMY8 #CheckpointBlockade #CancerImmunotherapy @wellerchen.bsky.social @Samuels-lab.bsky.social  @yardenasamuels.bsky.social

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...

✨ 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)

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)

Proud of my PhD student Nofar Gumpert giving an excellent talk at the #MICC conference un Athens!!!

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

Thrilled to share that our new paper on Macrophage Migration Inhibitory Factor (MIF) as a key regulator of immune evasion in melanoma, is now published in Cancer Discovery! Find the full study here: aacrjournals.org/cancerdiscov...