FGF2 alters macrophage polarization, tumour immunity and growth and can be targeted during radiotherapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32792542.
- Also identified by DOI 10.1038/s41467-020-17914-x and PMC identifier 7426415.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (FGF2<sup>LMW</sup>) regress dependent on T cells. Yet, TAMS not T cells express FGF receptors. Bone marrow derived-macrophages from Fgf2<sup>LMW-/-</sup> 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<sup>+</sup>/CD206<sup>+</sup> 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.
Medical subject headings
- Fibroblast Growth Factor 2
- Radiotherapy