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Updated: Jan 13, 2026

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

Published on: December 22, 2020

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Fibroblast activation protein promotes natural killer cell invasion and tumor infiltration

Rachael E Maynard1, Allison A Fitzgerald1, Emily F Marcisak2

  • 1Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States.

Journal of Immunology (Baltimore, Md. : 1950)
|October 28, 2025
PubMed

Insights

Fibroblast activation protein (FAP) is newly found on natural killer (NK) cells, enhancing their ability to infiltrate tumors. Engineering NK cells with FAP shows promise for improving cancer immunotherapy by boosting tumor cell killing.

Area of Science:

  • Immunology
  • Cancer Biology
  • Protease Function

Background:

  • Natural killer (NK) cells are crucial for immunity but struggle to infiltrate solid tumors, limiting their therapeutic use.
  • Fibroblast activation protein (FAP) was traditionally considered fibroblast-restricted.

Purpose of the Study:

  • To identify novel roles of FAP in NK cell biology.
  • To investigate FAP's impact on NK cell migration, invasion, and anti-tumor activity.

Main Methods:

  • Genetic knockout and overexpression of FAP in human NK cells.
  • In vitro assays for cell migration, extracellular matrix invasion, and tumor spheroid infiltration.
  • In vivo studies using mouse xenograft models.

Main Results:

  • FAP is identified as a novel surface protease on human NK cells.
  • FAP overexpression significantly enhanced NK cell migration, matrix invasion, and tumor infiltration.
  • FAP-engineered NK cells demonstrated superior tumor infiltration and reduced tumor burden in vivo.

Conclusions:

  • FAP plays a previously unrecognized role in regulating NK cell proteolytic functions.
  • Enhancing NK cell proteolytic migration via FAP engineering offers a promising strategy for improving cancer immunotherapies.
Keywords:
cancer immunotherapyextracellular matrix degradationfibroblast activation proteinnatural killer cellspancreatic cancer

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