Spatially Resolved Molecular Subtyping Uncovers Tumor Progression and Immune Evasion Mechanisms in High-Grade Serous Ovarian Cancer - PubMed
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- #molecular subtyping
- #spatial transcriptomics
- #immune evasion
- Spatially resolved molecular subtyping in HGSOC reveals five distinct gene programs (GP1-GP5) with specific spatial distributions and functional roles, such as invasion, proliferation, and immunoreactivity.
- Molecular subtypes exhibit dynamic spatial transitions that promote tumor progression; e.g., differentiated-proliferative dominates tumor cores, while differentiated-invasive localizes to invasive fronts driven by SDC4-expressing epithelial cells, which enhance migration/invasion.
- Immune evasion mechanisms involve co-localization of subtypes: differentiated-invasive and immunoreactive establish immunosuppression via TNFα-SAA1/2-APOE signaling, recruiting immunosuppressive myeloid cells, while mesenchymal and immunoreactive subtypes in omental metastases create fibroblast-derived collagen barriers and dysregulated chemokines to exclude immune infiltration.
- The study provides a mechanistic framework linking subtype spatial transitions to progression and co-localization to immune evasion, offering insights for targeting spatially organized tumor-immune interactions in HGSOC.