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Updated: Jun 14, 2026

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
06:35

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

Published on: December 22, 2020

Cancer-associated fibroblast subtypes differentially modulate natural killer cells in cancer

Leonor Nunes Rodrigues1, Hafsa Munir2, Ibone Thate Arrazola3

  • 1MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK; MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.

Cell Reports
|June 12, 2026
PubMed

Insights

Cancer-associated fibroblasts (CAFs) in pancreatic cancer suppress natural killer (NK) cell function. Specific CAF subtypes hinder NK cell infiltration and cytotoxicity, impacting immunotherapy potential.

Area of Science:

  • Immunology
  • Cancer Biology
  • Tumor Microenvironment

Background:

  • Natural killer (NK) cells are crucial for innate immunity against tumors.
  • The tumor microenvironment (TME) often suppresses NK cell activity.
  • Cancer-associated fibroblasts (CAFs) are key components of the pancreatic ductal adenocarcinoma (PDAC) TME, but their role in NK cell regulation is unclear.

Purpose of the Study:

  • To investigate the interplay between different cancer-associated fibroblast (CAF) subtypes and natural killer (NK) cells in pancreatic ductal adenocarcinoma (PDAC).
  • To understand how CAFs influence NK cell function, including cytotoxicity and tumor infiltration.

Main Methods:

  • Analysis of human pancreatic ductal adenocarcinoma (PDAC) samples.
  • Utilized mouse models of PDAC.
  • Performed functional assays to assess NK cell activity and interactions with CAFs.

Main Results:

  • Intratumoral NK cells in PDAC are immature.
  • Myofibroblastic CAFs (myCAFs), driven by TGF-β, significantly suppress NK cell function.
  • Inflammatory CAFs (iCAFs) have a different impact compared to myCAFs.
  • myCAF-rich areas showed reduced NK cell infiltration, suggesting impaired recruitment.
  • CAFs suppress NK cell cytotoxicity through direct contact and soluble factors like prostaglandin E2 (PGE2).

Conclusions:

  • Distinct CAF subpopulations exert differential effects on NK cell functions in PDAC.
  • Overcoming CAF-mediated suppression of NK cell cytotoxicity and infiltration is critical for effective immunotherapy.
  • Targeting CAFs may enhance the anti-tumoral capacity of NK cells in pancreatic cancer.
Keywords:
CAFCP: cancerCP: immunologyNK cellsPDACPGE2fibroblaststumor microenvironment

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