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The scar-forming cells of pancreatic cancer are not all the same: those touching the tumour cells make the dense fibrous tissue, while those further away pump out inflammatory signals such as IL-6.
Pancreatic stellate cells differentiate into cancer-associated fibroblasts that produce desmoplastic stroma, but whether subtypes exist was unknown. A CAF subpopulation with elevated alpha-smooth muscle actin was identified immediately adjacent to neoplastic cells in mouse and human tissue; co-culture of murine stellate cells with tumour organoids recapitulated it and showed these organoid-activated CAFs produce desmoplastic stroma. The co-cultures revealed a second subpopulation, located at a distance, lacking elevated alpha-SMA and secreting IL-6 and other inflammatory mediators; both were corroborated in mouse and human tissue.
The myCAF and iCAF distinction is why 'target the stroma' became 'target a fibroblast state', and IL-6 blockade combinations follow from it.
Shares Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF), David A. Tuveson, Cold Spring Harbor Laboratory, Fibroblast activation, desmoplasia & matrix stiffness.
Shares Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF), Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME).
Shares David A. Tuveson, Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), FAP, Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME), Pancreatic ductal adenocarcinoma.
Shares David A. Tuveson, FAP, Fibroblast activation, desmoplasia & matrix stiffness, Pancreatic ductal adenocarcinoma.
Shares Desmoplasia (tumour stroma), Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME), Pancreatic ductal adenocarcinoma.
Shares Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF), FAP, Fibroblast activation, desmoplasia & matrix stiffness, Tumour microenvironment (TME).