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Molecules. 2018 Dec 20;24(1). pii: E9. doi: 10.3390/molecules24010009.

Molecular Repolarisation of Tumour-Associated Macrophages.

Author information

1
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands. Floris.vanDalen@radboudumc.nl.
2
Department of Bio-Organic Chemistry, Institute for Complex Molecular Systems, Eindhoven University of Technology, 5600 MB Eindhoven, The Netherlands. M.H.M.E.v.Stevendaal@tue.nl.
3
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands. Felix.L.Fennemann@radboudumc.nl.
4
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands. Martijn.Verdoes@radboudumc.nl.
5
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands. Olga.Ilina@radboudumc.nl.

Abstract

The tumour microenvironment (TME) is composed of extracellular matrix and non-mutated cells supporting tumour growth and development. Tumour-associated macrophages (TAMs) are among the most abundant immune cells in the TME and are responsible for the onset of a smouldering inflammation. TAMs play a pivotal role in oncogenic processes as tumour proliferation, angiogenesis and metastasis, and they provide a barrier against the cytotoxic effector function of T lymphocytes and natural killer (NK) cells. However, TAMs are highly plastic cells that can adopt either pro- or anti-inflammatory roles in response to environmental cues. Consequently, TAMs represent an attractive target to recalibrate immune responses in the TME. Initial TAM-targeted strategies, such as macrophage depletion or disruption of TAM recruitment, have shown beneficial effects in preclinical models and clinical trials. Alternatively, reprogramming TAMs towards a proinflammatory and tumouricidal phenotype has become an attractive strategy in immunotherapy. This work summarises the molecular wheelwork of macrophage biology and presents an overview of molecular strategies to repolarise TAMs in immunotherapy.

KEYWORDS:

cancer immunotherapy; repolarisation; small molecules; tumour microenvironment; tumour-associated macrophages

PMID:
30577495
PMCID:
PMC6337345
DOI:
10.3390/molecules24010009
[Indexed for MEDLINE]
Free PMC Article

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