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dc.contributor.authorBrown, JS
dc.contributor.authorSundar, R
dc.contributor.authorLopez, J
dc.date.accessioned2017-11-22T16:00:48Z
dc.date.issued2018-02
dc.identifier.citationBritish journal of cancer, 2018, 118 (3), pp. 312 - 324
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/932
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/bjc.2017.376
dc.description.abstractThe idea that chemotherapy can be used in combination with immunotherapy may seem somewhat counterproductive, as it can theoretically eliminate the immune cells needed for antitumour immunity. However, much preclinical work has now demonstrated that in addition to direct cytotoxic effects on cancer cells, a proportion of DNA damaging agents may actually promote immunogenic cell death, alter the inflammatory milieu of the tumour microenvironment and/or stimulate neoantigen production, thereby activating an antitumour immune response. Some notable combinations have now moved forward into the clinic, showing promise in phase I-III trials, whereas others have proven toxic, and challenging to deliver. In this review, we discuss the emerging data of how DNA damaging agents can enhance the immunogenic properties of malignant cells, focussing especially on immunogenic cell death, and the expansion of neoantigen repertoires. We discuss how best to strategically combine DNA damaging therapeutics with immunotherapy, and the challenges of successfully delivering these combination regimens to patients. With an overwhelming number of chemotherapy/immunotherapy combination trials in process, clear hypothesis-driven trials are needed to refine the choice of combinations, and determine the timing and sequencing of agents in order to stimulate antitumour immunological memory and improve maintained durable response rates, with minimal toxicity.
dc.formatPrint-Electronic
dc.format.extent312 - 324
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectAnimals
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectDNA Damage
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectAntigens, Neoplasm
dc.subjectImmunotherapy
dc.subjectSignal Transduction
dc.subjectImmunologic Surveillance
dc.subjectDNA Repair
dc.subjectTumor Microenvironment
dc.subjectCTLA-4 Antigen
dc.subjectProgrammed Cell Death 1 Receptor
dc.subjectB7-H1 Antigen
dc.titleCombining DNA damaging therapeutics with immunotherapy: more haste, less speed.
dc.typeJournal Article
dcterms.dateAccepted2017-09-04
rioxxterms.versionofrecord10.1038/bjc.2017.376
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-02
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue3
pubs.notesNot 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 Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine (de Bono Prostate)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
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 Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine (de Bono Prostate)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume118
pubs.embargo.termsNot known
icr.researchteamMedicine (de Bono Prostate)en_US
dc.contributor.icrauthorLopez, Juanitaen
dc.contributor.icrauthorMarsden,en


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