P1.074. SNORD33-Driven 18S rRNA 2′-O-Methylation Licenses TNFSF9–4-1BB Signaling and Sensitizes ESCC to PD-1 Blockade

Clicks: 16
ID: 326108
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #417 of 453 articles by views in diseases of the esophagus : official journal of the international society for diseases of the esophagus

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 453 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Abstract Topic Esophageal Cancer: Adjuvant and Neo-Adjuvant Therapies Background Neoadjuvant PD-1/PD-L1 based immunotherapy improve outcomes for resectable esophageal squamous cell carcinoma (ESCC), but patient outcome are heterogeneous and robust pretreatment blood biomarkers are lacking. Methods We performed an unbiased plasma snoRNA screen (359 snoRNAs) and quantified SNORD33 in two independent neoadjuvant immunotherapy cohorts (training N = 62; validation N =33). Mechanistic studies integrated scRNA-seq of post-treatment specimens (N = 6), tumor-cell SNORD33 perturbation in syngeneic models under anti–PD-1, paired RNA-seq/TMT proteomics, RNA-FISH, RTL-P, polysome profiling, and 4-1BB agonism; multiplex RNA-FISH/IF assessed human tissues. Results SNORD33 was prioritized in discovery screening and, clinically, baseline plasma SNORD33 was higher in ypCR, inversely correlated with tumor regression grade, and predicted ypCR (AUC 0.815 and 0.767 in training and validation). SNORD33 high tumors showed increased NK cells/neutrophils and an activated NK program. Tumor-cell SNORD33 loss blunted anti–PD-1 efficacy, reduced intratumoral NK accumulation, and impaired NK effector features with increased inhibitory receptors. Multi-omics prioritized TNFSF9 (4-1BBL) as a SNORD33-dependent output with transcript–protein discordance; SNORD33 localized to nucleoli, modulated 18S rRNA U1326 2′-O-methylation, and promoted TNFSF9 translation. Agonistic 4-1BB restored anti–PD-1 tumor control, and human multiplex RNA-FISH/IF showed SNORD33–TNFSF9 proximity with effective NK enrichment. Conclusion Plasma SNORD33 is a clinically tractable pretreatment biomarker and defines a ribosome-centered SNORD33–TNFSF9–4-1BB axis linking rRNA modification to NK-dependent checkpoint sensitivity, supporting biomarker-guided 4-1BB–based combinations in ESCC.
Reference Key
openalex_W7203984845 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Runze You, Xu Huang, Lijie Tan
Are you one of these authors? Claim your profile
Journal diseases of the esophagus : official journal of the international society for diseases of the esophagus
Year 2026
DOI
10.1093/dote/doag077.222
URL
https://doi.org/10.1093/dote/doag077.222
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.