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dc.contributor.authorKottke, T
dc.contributor.authorEvgin, L
dc.contributor.authorShim, KG
dc.contributor.authorRommelfanger, D
dc.contributor.authorBoisgerault, N
dc.contributor.authorZaidi, S
dc.contributor.authorDiaz, RM
dc.contributor.authorThompson, J
dc.contributor.authorIlett, E
dc.contributor.authorCoffey, M
dc.contributor.authorSelby, P
dc.contributor.authorPandha, H
dc.contributor.authorHarrington, K
dc.contributor.authorMelcher, A
dc.contributor.authorVile, R
dc.date.accessioned2017-10-23T15:17:22Z
dc.date.issued2017-11
dc.identifier.citationCancer immunology research, 2017, 5 (11), pp. 1029 - 1045
dc.identifier.issn2326-6066
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/854
dc.identifier.eissn2326-6074
dc.identifier.doi10.1158/2326-6066.cir-17-0175
dc.description.abstractUnderstanding how incompletely cleared primary tumors transition from minimal residual disease (MRD) into treatment-resistant, immune-invisible recurrences has major clinical significance. We show here that this transition is mediated through the subversion of two key elements of innate immunosurveillance. In the first, the role of TNFα changes from an antitumor effector against primary tumors into a growth promoter for MRD. Second, whereas primary tumors induced a natural killer (NK)-mediated cytokine response characterized by low IL6 and elevated IFNγ, PD-L1hi MRD cells promoted the secretion of IL6 but minimal IFNγ, inhibiting both NK-cell and T-cell surveillance. Tumor recurrence was promoted by trauma- or infection-like stimuli inducing VEGF and TNFα, which stimulated the growth of MRD tumors. Finally, therapies that blocked PD-1, TNFα, or NK cells delayed or prevented recurrence. These data show how innate immunosurveillance mechanisms, which control infection and growth of primary tumors, are exploited by recurrent, competent tumors and identify therapeutic targets in patients with MRD known to be at high risk of relapse. Cancer Immunol Res; 5(11); 1029-45. ©2017 AACR.
dc.formatPrint-Electronic
dc.format.extent1029 - 1045
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.subjectKiller Cells, Natural
dc.subjectT-Lymphocytes
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectMice, Transgenic
dc.subjectReoviridae
dc.subjectMelanoma, Experimental
dc.subjectSkin Neoplasms
dc.subjectNeoplasm Recurrence, Local
dc.subjectPaclitaxel
dc.subjectGanciclovir
dc.subjectTumor Necrosis Factor-alpha
dc.subjectAntibodies
dc.subjectCytokines
dc.subjectImmunologic Surveillance
dc.subjectFemale
dc.subjectOncolytic Virotherapy
dc.titleSubversion of NK-cell and TNFα Immune Surveillance Drives Tumor Recurrence.
dc.typeJournal Article
dcterms.dateAccepted2017-10-03
rioxxterms.funderThe Institute of Cancer Research
rioxxterms.identifier.projectUnspecified
rioxxterms.versionofrecord10.1158/2326-6066.cir-17-0175
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-11
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer immunology research
pubs.issue11
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 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-statusPublished
pubs.volume5
pubs.embargo.termsNot known
icr.researchteamTargeted Therapyen_US
icr.researchteamTranslational Immunotherapyen_US
dc.contributor.icrauthorHarrington, Kevinen
dc.contributor.icrauthorZaidi, Shane Haideren
dc.contributor.icrauthorMelcher, Alanen


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