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

Author

Listed:
  • Jae Hong Im

    (University of Oxford)

  • Jon N. Buzzelli

    (University of Oxford)

  • Keaton Jones

    (University of Oxford)

  • Fanny Franchini

    (The Kennedy Institute of Rheumatology)

  • Alex Gordon-Weeks

    (University of Oxford)

  • Bostjan Markelc

    (University of Oxford)

  • Jianzhou Chen

    (University of Oxford)

  • Jin Kim

    (Galaxy Biotech)

  • Yunhong Cao

    (University of Oxford)

  • Ruth J. Muschel

    (University of Oxford)

Abstract

Regulation of the programming of tumour-associated macrophages (TAMs) controls tumour growth and anti-tumour immunity. We examined the role of FGF2 in that regulation. Tumours in mice genetically deficient in low-molecular weight FGF2 (FGF2LMW) regress dependent on T cells. Yet, TAMS not T cells express FGF receptors. Bone marrow derived-macrophages from Fgf2LMW−/− mice co-injected with cancer cells reduce tumour growth and express more inflammatory cytokines. FGF2 is induced in the tumour microenvironment following fractionated radiation in murine tumours consistent with clinical reports. Combination treatment of in vivo tumours with fractionated radiation and a blocking antibody to FGF2 prolongs tumour growth delay, increases long-term survival and leads to a higher iNOS+/CD206+ TAM ratio compared to irradiation alone. These studies show for the first time that FGF2 affects macrophage programming and is a critical regulator of immunity in the tumour microenvironment.

Suggested Citation

  • Jae Hong Im & Jon N. Buzzelli & Keaton Jones & Fanny Franchini & Alex Gordon-Weeks & Bostjan Markelc & Jianzhou Chen & Jin Kim & Yunhong Cao & Ruth J. Muschel, 2020. "FGF2 alters macrophage polarization, tumour immunity and growth and can be targeted during radiotherapy," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17914-x
    DOI: 10.1038/s41467-020-17914-x
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    Cited by:

    1. JungHo Kong & Doyeon Ha & Juhun Lee & Inhae Kim & Minhyuk Park & Sin-Hyeog Im & Kunyoo Shin & Sanguk Kim, 2022. "Network-based machine learning approach to predict immunotherapy response in cancer patients," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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