# Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer

Source: https://onco.cc/key-papers/paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017/  
OnCo record `paper-ohlund-caf-subtypes-mycaf-icaf-jem-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Journal of Experimental Medicine
- Year: 2017
- DOI: 10.1084/jem.20162024
- Authors: Ohlund D, Handly-Santana A, Biffi G, et al.
- 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.
- What it means: 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.

## Sources

- Ohlund et al., J Exp Med 2017: myofibroblastic and inflammatory fibroblasts (myCAF, iCAF): https://doi.org/10.1084/jem.20162024
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28232471/

## Connected records

- cancers: [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Patient-derived organoids](https://onco.cc/technologies/organoids/)
- targets: [FAP](https://onco.cc/targets/fap/), [Interleukin-6 and IL-6 receptor](https://onco.cc/targets/il6/)
- institutions: [Cold Spring Harbor Laboratory](https://onco.cc/institutions/cold-spring-harbor/)
- 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/), [Fibroblast subtypes in the pancreatic cancer stroma (myCAF, iCAF and apCAF)](https://onco.cc/terms/caf-subtypes-pancreatic/)
- people: [David A. Tuveson](https://onco.cc/people/david-tuveson/)

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