ArticleGastroenterology2026
Targeting Oncomucin-Driven Immunosuppression Improves the Efficacy of K-ras
Article in Gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Unique N-glycoproteomics and phosphoproteomics of mucins predict clinical outcomes in pancreatic ductal adenocarcinoma.Cancer letters · 2026Article
- RAS signaling and remodeling of the immune microenvironment in pancreatic ductal adenocarcinoma: implications of emerging RAS-targeted therapy.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
17 authors.
Funding
Abstract
BACKGROUND &
aimsOncogenic de novo mucins (oncoMUCs; MUC4, MUC16, and MUC5AC) are progressively upregulated in pancreatic ductal adenocarcinoma (PDA). Although their individual cell-intrinsic roles have been investigated, their collective impact on PDA progression and the tumor microenvironment (TME) remains unclear. Evaluating the patient-centric impact of oncoMUCs on the TME will inform diagnostic and therapeutic strategies.
methodsIntegration of single-cell RNA sequencing (n = 34), multiplex/sequential immunostaining, and murine models characterized the oncomucinome. Immune suppression was investigated using NanoString profiling and gene silencing. Pharmacologic oncoMUC targeting (Istradefylline) was evaluated in combination with K-ras
resultsOncoMUCs showed extensive clonal diversity and survival disadvantage (P = .00013) in PDA. OncoMUC4 and oncoMUC16 subpopulations were enriched after stage IIA/B, and their deletion significantly reduced immune checkpoints (ICs) expression (V-domain immunoglobulin suppressor of T-cell activation [VISTA]: P < .0001, .001; T-cell immunoglobulin and mucin domain-containing protein 3 [TIM3]: P < .0001, .001), and increased CD8
conclusionsTransmembrane oncoMUCs promote immune evasion in PDA through EGFR/UNC5B signaling, and their targeting enhances the efficacy of K-ras
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