Molecular repolarisation of tumour-associated macrophages

Floris J. van Dalen, Marleen H.M.E. van Stevendaal, Felix L. Fennemann, Martijn Verdoes (Corresponding author), Olga Ilina

Research output: Contribution to journalReview articleAcademicpeer-review

10 Citations (Scopus)

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 proor 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.

LanguageEnglish
Article number9
Number of pages25
JournalMolecules
Volume24
Issue number1
DOIs
StatePublished - 1 Jan 2019

Fingerprint

macrophages
Macrophages
Tumors
tumors
Neoplasms
Tumor Microenvironment
Immunotherapy
cells
smoldering
effectors
angiogenesis
Growth and Development
Natural Killer Cells
phenotype
Plastics
T-cells
Cues
Extracellular Matrix
lymphocytes
cues

Keywords

  • Cancer immunotherapy
  • Repolarisation
  • Small molecules
  • Tumour microenvironment
  • Tumour-associated macrophages

Cite this

van Dalen, F. J., van Stevendaal, M. H. M. E., Fennemann, F. L., Verdoes, M., & Ilina, O. (2019). Molecular repolarisation of tumour-associated macrophages. Molecules, 24(1), [9]. DOI: 10.3390/molecules24010009
van Dalen, Floris J. ; van Stevendaal, Marleen H.M.E. ; Fennemann, Felix L. ; Verdoes, Martijn ; Ilina, Olga. / Molecular repolarisation of tumour-associated macrophages. In: Molecules. 2019 ; Vol. 24, No. 1.
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van Dalen, FJ, van Stevendaal, MHME, Fennemann, FL, Verdoes, M & Ilina, O 2019, 'Molecular repolarisation of tumour-associated macrophages' Molecules, vol. 24, no. 1, 9. DOI: 10.3390/molecules24010009

Molecular repolarisation of tumour-associated macrophages. / van Dalen, Floris J.; van Stevendaal, Marleen H.M.E.; Fennemann, Felix L.; Verdoes, Martijn (Corresponding author); Ilina, Olga.

In: Molecules, Vol. 24, No. 1, 9, 01.01.2019.

Research output: Contribution to journalReview articleAcademicpeer-review

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N2 - 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 proor 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.

AB - 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 proor 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.

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van Dalen FJ, van Stevendaal MHME, Fennemann FL, Verdoes M, Ilina O. Molecular repolarisation of tumour-associated macrophages. Molecules. 2019 Jan 1;24(1). 9. Available from, DOI: 10.3390/molecules24010009