Reading view
Spatial multi-omics defines cancer-associated fibroblasts subtype gradients driving metabolic support and immune remodeling in pancreatic ductal adenocarcinoma
Cancer Lett. 2026 May 16;653:218585. doi: 10.1016/j.canlet.2026.218585. Online ahead of print.
ABSTRACT
Pancreatic ductal adenocarcinoma is characterized by a fibrotic and metabolically active tumor microenvironment where cancer-associated fibroblasts (CAFs) mediate metabolic crosstalk, extracellular matrix (ECM) remodeling, and immune regulation. However, the metabolic and spatial heterogeneity of CAFs remains incompletely understood. We integrated spatial transcriptomics and spatial metabolomics data from PDAC tissues and performed SpatialGlue-based multimodal clustering to define CAF subtypes. To characterize metabolic communication, we developed an optimal transport (OT)-based metabolic inference framework to quantitatively model metabolite association between CAFs and tumor cells. Subtype-specific features were independently validated using an independent spatial metabolomics cohort and multiplex immunofluorescence (mIHC) staining. Furthermore, these features were correlated with clinical outcomes via TCGA-PAAD deconvolution. Spatial multi-omics integration identified three robust CAF subtypes with distinct signatures. OT analysis revealed differential metabolic interactions: CAF_C0 mediated amino acid/peptide transfer, CAF_C1 was the primary source of lipids, while CAF_C2 exhibited limited metabolic association but stronger immune and ECM signaling activity. Deconvolution confirmed that CAF composition was strongly associated with prognosis; CAF_C2 enrichment predicted poorer survival and gemcitabine resistance, whereas a higher CAF_C0/CAF_C1 balance correlated with improved outcomes. By combining spatial multi-omics with OT-based modeling, this study delineates metabolically and spatially distinct CAF states with clinical relevance. Our findings suggest CAFs act as both metabolic donors and immune-ECM regulators, providing new insights into stromal reprogramming and potential subtype-specific therapeutic targets in PDAC.
PMID:42144098 | DOI:10.1016/j.canlet.2026.218585
Runtime Burden Allocation for Structured LLM Routing in Agentic Expert Systems: A Full-Factorial Cross-Backend Methodology
Do Phone-Use Agents Respect Your Privacy?
Physiological and Semantic Patterns in Medical Teams Using an Intelligent Tutoring System
Downsides of Smartness Across Edge-Cloud Continuum in Modern Industry
Understanding vs. Generation: Navigating Optimization Dilemma in Multimodal Models
UniQueR: Unified Query-based Feedforward 3D Reconstruction
Effects of multisensory stimulation based on immersive virtual reality in postoperative neuropsychiatric recovery after gynecological laparoscopy
npj Digital Medicine, Published online: 24 March 2026; doi:10.1038/s41746-026-02515-7
Effects of multisensory stimulation based on immersive virtual reality in postoperative neuropsychiatric recovery after gynecological laparoscopyComputational analysis of multi-omics data reveals CXCL10(+) DC-Treg interaction drives immunosuppressive microenvironment in AFP-positive hepatocellular carcinoma
Cell Mol Life Sci. 2026 Mar 19. doi: 10.1007/s00018-026-06167-4. Online ahead of print.
NO ABSTRACT
PMID:41854876 | DOI:10.1007/s00018-026-06167-4