dc.contributor.author | Wilkins, A | |
dc.contributor.author | McDonald, F | |
dc.contributor.author | Harrington, K | |
dc.contributor.author | Melcher, A | |
dc.date.accessioned | 2019-03-26T11:11:28Z | |
dc.date.issued | 2019-03-06 | |
dc.identifier.citation | Journal for immunotherapy of cancer, 2019, 7 (1), pp. 64 - ? | |
dc.identifier.issn | 2051-1426 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3161 | |
dc.identifier.eissn | 2051-1426 | |
dc.identifier.doi | 10.1186/s40425-019-0542-z | |
dc.description.abstract | Formenti et al. have recently reported the clinical outcomes and translational readouts of a trial of the anti-CTLA-4 inhibitor, ipilimumab, in combination with palliative radiotherapy in 39 patients with non-small cell lung cancer. A radiological response was seen in 18% of patients and 31% of patients experienced disease control. These clinical outcomes appear to be superior to historical studies using ipilimumab alone and suggest that radiation may have triggered systemic, so-called abscopal, immune responses in some patients. Induction of interferon-beta (IFN-β) and maximal expansion and contraction of distinct T cell receptor clones were the most significant factors predicting response. Importantly, established predictive biomarkers of response to immunotherapy alone, including the expression of PD-L1 in diagnostic biopsies and tumour mutational burden, did not predict response. The report provides important human qualification of pre-clinical mechanistic insights indicating that abscopal responses can be generated with optimised radiotherapy fractionation schedules and anti-CTLA-4 inhibition. Additionally, an intriguing mechanism by which radiation can be immunogenic is described, namely radiation-induced transcriptional upregulation of neo-antigens. | |
dc.format | Electronic | |
dc.format.extent | 64 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BMC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Carcinoma, Non-Small-Cell Lung | |
dc.subject | Lung Neoplasms | |
dc.subject | Antibodies, Monoclonal | |
dc.subject | CTLA-4 Antigen | |
dc.subject | Ipilimumab | |
dc.title | Radiotherapy enhances responses of lung cancer to CTLA-4 blockade. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-02-20 | |
rioxxterms.versionofrecord | 10.1186/s40425-019-0542-z | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2019-03-06 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal for immunotherapy of cancer | |
pubs.issue | 1 | |
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.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 | 7 | |
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 | |