dc.contributor.author | Wilkins, AC | |
dc.contributor.author | Patin, EC | |
dc.contributor.author | Harrington, KJ | |
dc.contributor.author | Melcher, AA | |
dc.date.accessioned | 2019-01-30T11:29:09Z | |
dc.date.issued | 2019-04-01 | |
dc.identifier.citation | The Journal of pathology, 2019, 247 (5), pp. 606 - 614 | |
dc.identifier.issn | 0022-3417 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3035 | |
dc.identifier.eissn | 1096-9896 | |
dc.identifier.doi | 10.1002/path.5232 | |
dc.description.abstract | Historically, our understanding of the cytotoxicity of radiation has centred on tumour cell-autonomous mechanisms of cell death. Here, tumour cell death occurs when a threshold number of radiation-induced non-reparable double-stranded DNA breaks is exceeded. However, in recent years, the importance of immune mechanisms of cell death has been increasingly recognised, as well as the impact of radiotherapy on non-malignant cellular components of the tumour microenvironment. Conserved antiviral pathways that detect foreign nucleic acid in the cytosol and drive downstream interferon (IFN) responses via the cyclic guanosine monophosphate-adenosine monophosphate synthase/stimulator of IFN genes (cGAS/STING) pathway are key components of the immune response to radiation-induced DNA damage. In preclinical models, acute induction of a type 1 IFN response is important for both direct and abscopal tumour responses to radiation. Inhibitors of the DNA damage response show promise in augmenting this inflammatory IFN response. However, a substantial proportion of tumours show chronic IFN signalling prior to radiotherapy, which paradoxically drives immunosuppression. This chronic IFN signalling leads to treatment resistance, and heterotypic interactions between stromal fibroblasts and tumour cells contribute to an aggressive tumour phenotype. The effect of radiotherapy on myeloid cell populations, particularly tumour-associated macrophages, has an additional impact on the immune tumour microenvironment. It is not yet clear how the above preclinical findings translate into a human context. Human tumours show greater intratumoural genomic heterogeneity and more variable levels of chromosomal instability than experimental murine models. High-quality translational studies of immunological changes occurring during radiotherapy that incorporate intrinsic tumour biology will enable a better understanding of the immunological consequences of radiation-induced DNA damage in patients. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. | |
dc.format | Print-Electronic | |
dc.format.extent | 606 - 614 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | WILEY | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | CD8-Positive T-Lymphocytes | |
dc.subject | Myeloid Cells | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Neoplasms | |
dc.subject | DNA Damage | |
dc.subject | Disease Models, Animal | |
dc.subject | Chromosomal Instability | |
dc.subject | Interferon Type I | |
dc.subject | Immunologic Factors | |
dc.subject | Antigens, Neoplasm | |
dc.subject | Combined Modality Therapy | |
dc.subject | Radiation Dosage | |
dc.subject | Signal Transduction | |
dc.subject | Immune Tolerance | |
dc.subject | Cancer-Associated Fibroblasts | |
dc.title | The immunological consequences of radiation-induced DNA damage. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-01-07 | |
rioxxterms.versionofrecord | 10.1002/path.5232 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2019-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | The Journal of pathology | |
pubs.issue | 5 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy/Translational Immunotherapy (TL) | |
pubs.publication-status | Published | |
pubs.volume | 247 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Targeted Therapy | |
icr.researchteam | Translational Immunotherapy | |
dc.contributor.icrauthor | Corbett, Anna | |
dc.contributor.icrauthor | Harrington, Kevin | |
dc.contributor.icrauthor | Melcher, Alan | |