{"entity":{"id":"paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017","kind":"paper","name":"Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer","aka":[],"tldr":"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.","summary":"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.","asOf":"2026-09-24","links":[{"label":"Ohlund et al., J Exp Med 2017: myofibroblastic and inflammatory fibroblasts (myCAF, iCAF)","url":"https://doi.org/10.1084/jem.20162024"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28232471/"}],"tags":[],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["organoids"],"targets":["il6","fap"],"drugs":[],"companies":[],"institutions":["cold-spring-harbor"],"pathways":["caf-activation-desmoplasia","tumor-microenvironment"],"terms":["desmoplasia"],"trials":[],"people":["david-tuveson"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Journal of Experimental Medicine","year":2017,"doi":"10.1084/jem.20162024","pmid":"28232471","authors":"Ohlund D, Handly-Santana A, Biffi G, et al.","paperType":"basic","findings":["Myofibroblastic CAFs (alpha-SMA high) sit next to tumour cells and build the stroma.","Inflammatory CAFs sit further away and secrete IL-6 and other mediators."],"whatItMeans":"The myCAF and iCAF distinction is why 'target the stroma' became 'target a fibroblast state', and IL-6 blockade combinations follow from it.","caveats":["Organoid co-culture and mouse models.","Subtypes are states rather than fixed lineages."],"changedPractice":false},"route":"/key-papers/paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017/","neighbours":{"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"organoids","kind":"technology","name":"Patient-derived organoids","route":"/technologies/organoids/"}],"target":[{"id":"fap","kind":"target","name":"FAP","route":"/targets/fap/"},{"id":"il6","kind":"target","name":"Interleukin-6 and IL-6 receptor","route":"/targets/il6/"}],"institution":[{"id":"cold-spring-harbor","kind":"institution","name":"Cold Spring Harbor Laboratory","route":"/institutions/cold-spring-harbor/"}],"pathway":[{"id":"caf-activation-desmoplasia","kind":"pathway","name":"Fibroblast activation, desmoplasia & matrix stiffness","route":"/pathways/caf-activation-desmoplasia/"},{"id":"tumor-microenvironment","kind":"pathway","name":"Tumour microenvironment (TME)","route":"/pathways/tumor-microenvironment/"}],"term":[{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","route":"/terms/desmoplasia/"},{"id":"caf-subtypes-pancreatic","kind":"term","name":"Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF)","route":"/terms/caf-subtypes-pancreatic/"}],"person":[{"id":"david-tuveson","kind":"person","name":"David A. Tuveson","route":"/people/david-tuveson/"}]}}