# Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF)

Source: https://onco.cc/terms/caf-subtypes-pancreatic/  
OnCo record `caf-subtypes-pancreatic` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-24
- Also known as: CAF subtypes; myCAF; iCAF; apCAF; Myofibroblastic CAF; Inflammatory CAF; Antigen-presenting CAF
- Tags: pancreatic-molecular

## Sources

- Ohlund et al., J Exp Med 2017: myofibroblastic and inflammatory fibroblasts (myCAF, iCAF): https://doi.org/10.1084/jem.20162024
- Elyada et al., Cancer Discov 2019: antigen-presenting fibroblasts by single-cell sequencing: https://doi.org/10.1158/2159-8290.CD-19-0094
- Grunwald et al., Cell 2021: spatially confined sub-tumour microenvironments: https://doi.org/10.1016/j.cell.2021.09.022

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Patient-derived organoids](https://onco.cc/technologies/organoids/), [Single-cell & spatial profiling](https://onco.cc/technologies/single-cell-spatial/), [Spatial transcriptomics](https://onco.cc/technologies/spatial-transcriptomics/)
- pathways: [Fibroblast activation, desmoplasia & matrix stiffness](https://onco.cc/pathways/caf-activation-desmoplasia/), [Tumour microenvironment (TME)](https://onco.cc/pathways/tumor-microenvironment/)
- terms: [Desmoplasia (tumour stroma)](https://onco.cc/terms/desmoplasia/), [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Immune exclusion](https://onco.cc/terms/immune-exclusion/)
- key papers: [Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts](https://onco.cc/key-papers/paper-elyada-antigen-presenting-cafs-single-cell-cancer-discov-2019/), [Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer](https://onco.cc/key-papers/paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017/), [Spatially confined sub-tumor microenvironments in pancreatic cancer](https://onco.cc/key-papers/paper-grunwald-subtme-pancreatic-cell-2021/)

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