{"entity":{"id":"caf-subtypes-pancreatic","kind":"term","name":"Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF)","aka":["CAF subtypes","myCAF","iCAF","apCAF","Myofibroblastic CAF","Inflammatory CAF","Antigen-presenting CAF"],"tldr":"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.","summary":"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.","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":"Elyada et al., Cancer Discov 2019: antigen-presenting fibroblasts by single-cell sequencing","url":"https://doi.org/10.1158/2159-8290.CD-19-0094"},{"label":"Grunwald et al., Cell 2021: spatially confined sub-tumour microenvironments","url":"https://doi.org/10.1016/j.cell.2021.09.022"}],"tags":["pancreatic-molecular"],"related":[],"cancers":["pancreatic"],"sections":[],"technologies":["single-cell-spatial","spatial-transcriptomics","organoids"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["caf-activation-desmoplasia","tumor-microenvironment"],"terms":["desmoplasia","immune-exclusion","cold-vs-hot"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017","paper-elyada-antigen-presenting-cafs-single-cell-cancer-discov-2019","paper-grunwald-subtme-pancreatic-cell-2021"],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},"route":"/terms/caf-subtypes-pancreatic/","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/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"},{"id":"spatial-transcriptomics","kind":"technology","name":"Spatial transcriptomics","route":"/technologies/spatial-transcriptomics/"}],"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":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"immune-exclusion","kind":"term","name":"Immune exclusion","route":"/terms/immune-exclusion/"}],"paper":[{"id":"paper-elyada-antigen-presenting-cafs-single-cell-cancer-discov-2019","kind":"paper","name":"Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts","route":"/key-papers/paper-elyada-antigen-presenting-cafs-single-cell-cancer-discov-2019/"},{"id":"paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017","kind":"paper","name":"Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer","route":"/key-papers/paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017/"},{"id":"paper-grunwald-subtme-pancreatic-cell-2021","kind":"paper","name":"Spatially confined sub-tumor microenvironments in pancreatic cancer","route":"/key-papers/paper-grunwald-subtme-pancreatic-cell-2021/"}]}}