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Inflammatory microenvironment remodelling by tumour cells after radiotherapy.

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Date
2020-04
ICR Author
Dillon, Magnus
McLaughlin, Martin
Corbett, Anna
Harrington, Kevin
Melcher, Alan
Pedersen, Malin
Wilkins, Anna
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Author
McLaughlin, M
Patin, EC
Pedersen, M
Wilkins, A
Dillon, MT
Melcher, AA
Harrington, KJ
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Type
Journal Article
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Abstract
The development of immune checkpoint inhibitors (ICIs) is revolutionizing the way we think about cancer treatment. Even so, for most types of cancer, only a minority of patients currently benefit from ICI therapies. Intrinsic and acquired resistance to ICIs has focused research towards new combination therapy approaches that seek to increase response rates, the depth of remission and the durability of benefit. In this Review, we describe how radiotherapy, through its immunomodulating effects, represents a promising combination partner with ICIs. We describe how recent research on DNA damage response (DDR) inhibitors in combination with radiotherapy may be used to augment this approach. Radiotherapy can kill cancer cells while simultaneously triggering the release of pro-inflammatory mediators and increasing tumour-infiltrating immune cells - phenomena often described colloquially as turning immunologically 'cold' tumours 'hot'. Here, we focus on new developments illustrating the key role of tumour cell-autonomous signalling after radiotherapy. Radiotherapy-induced tumour cell micronuclei activate cytosolic nucleic acid sensor pathways, such as cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), and propagation of the resulting inflammatory signals remodels the immune contexture of the tumour microenvironment. In parallel, radiation can impact immunosurveillance by modulating neoantigen expression. Finally, we highlight how tumour cell-autonomous mechanisms might be exploited by combining DDR inhibitors, ICIs and radiotherapy.
URI
https://repository.icr.ac.uk/handle/internal/3630
DOI
https://doi.org/10.1038/s41568-020-0246-1
Collections
  • Cancer Biology
  • Radiotherapy and Imaging
Subject
Animals
Humans
Neoplasms
Disease Susceptibility
Caspases
Nucleotidyltransferases
Membrane Proteins
Radiotherapy
Signal Transduction
Antigen Presentation
DNA Repair
Protein Processing, Post-Translational
Exosomes
Molecular Targeted Therapy
Tumor Microenvironment
Biomarkers, Tumor
Research team
Targeted Therapy
Translational Immunotherapy
Language
eng
Date accepted
2020-02-12
License start date
2020-04
Citation
Nature reviews. Cancer, 2020, 20 (4), pp. 203 - 217

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