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The fibroblasts that make up most of a pancreatic tumour are not one cell type. Those pressed against the cancer cells become contractile myofibroblasts (myCAF), those further away secrete inflammatory signals (iCAF), and a third group carries antigen-presenting molecules (apCAF). The states are plastic, which is why stripping the stroma out failed and reprogramming it is the current idea.
Ohlund and colleagues (2017) showed in pancreatic organoid and mouse co-cultures that cancer-associated fibroblasts take two states: myofibroblastic CAFs, alpha-smooth muscle actin-high, sit next to the tumour cells and lay down matrix, while inflammatory CAFs, further away, secrete interleukin-6 and other cytokines; the states are interconvertible depending on contact with cancer cells. Single-cell sequencing of human and mouse tumours added antigen-presenting CAFs expressing MHC class II, and confirmed the myCAF and iCAF programmes in patients (Elyada 2019). Spatial work then organised the tissue into reactive (immune-hot) and deserted (chemoprotective) sub-tumour microenvironments that shift under chemotherapy (Grunwald 2021). The clinical reading is on the record: depleting myofibroblasts or hedgehog signalling made tumours more aggressive in mice and hyaluronan degradation raised response without changing survival in phase 3, so the stroma is now read as a set of cell states to be redirected rather than a barrier to be removed.
Showing the technology this term belongs to: Single-cell & spatial profiling.
It explains why one biopsy can mislead and why chemotherapy selects for the protective neighbourhood, an argument for spatial rather than bulk profiling.
Fibroblasts are part of the immune conversation, not just a physical barrier, which is why stromal and immune strategies are now designed together.
The myCAF and iCAF distinction is why 'target the stroma' became 'target a fibroblast state', and IL-6 blockade combinations follow from it.
Shares Pancreatic ductal adenocarcinoma and the tag pancreatic-molecular.
Shares Pancreatic ductal adenocarcinoma and the tag pancreatic-molecular.
Shares Pancreatic ductal adenocarcinoma and the tag pancreatic-molecular.
Shares Pancreatic ductal adenocarcinoma and the tag pancreatic-molecular.
Shares Pancreatic ductal adenocarcinoma and the tag pancreatic-molecular.
Shares Pancreatic ductal adenocarcinoma and the tag pancreatic-molecular.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME), Hot vs cold tumours.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Single-cell & spatial profiling, Pancreatic ductal adenocarcinoma.