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FGF2 alters macrophage polarization, tumour immunity and growth and can be targeted during radiotherapy

Jae Hong Im1, Jon N Buzzelli1, Keaton Jones1

  • 1Oxford Institute for Radiation Oncology, University of Oxford, Oxford, OX3 7DQ, UK.

Nature Communications
|August 15, 2020
PubMed

Insights

Fibroblast Growth Factor 2 (FGF2) influences tumour-associated macrophage (TAM) programming, impacting anti-tumour immunity. Blocking FGF2 alongside radiation therapy enhances anti-tumour responses and survival.

Area of Science:

  • Immunology
  • Cancer Biology
  • Macrophage Biology

Background:

  • Tumour-associated macrophages (TAMs) play a critical role in regulating tumour growth and anti-tumour immunity.
  • The precise mechanisms by which TAMs are programmed within the tumour microenvironment are not fully understood.

Purpose of the Study:

  • To investigate the role of Fibroblast Growth Factor 2 (FGF2) in the programming of TAMs.
  • To determine if FGF2 is a viable therapeutic target for enhancing anti-tumour immunity.

Main Methods:

  • Utilized genetically modified mice deficient in low-molecular weight FGF2 (FGF2LMW-/-).
  • Assessed tumour growth, T cell responses, and macrophage cytokine production in vivo and ex vivo.
  • Administered fractionated radiation and FGF2-blocking antibodies in combination therapy models.

Main Results:

  • Tumours in FGF2LMW-/- mice showed T cell-dependent regression.
  • Macrophages from FGF2LMW-/- mice exhibited reduced tumour growth and increased inflammatory cytokine production.
  • Combination therapy with radiation and FGF2 blockade prolonged tumour growth delay and improved survival.
  • Fractionated radiation induced FGF2 in the tumour microenvironment.
  • Combination therapy increased the iNOS+/CD206+ TAM ratio.

Conclusions:

  • FGF2 significantly influences macrophage programming within the tumour microenvironment.
  • FGF2 is a critical regulator of anti-tumour immunity.
  • Targeting FGF2 in combination with radiation represents a promising strategy for cancer immunotherapy.

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