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dc.contributor.authorWennerberg, E
dc.contributor.authorSpada, S
dc.contributor.authorRudqvist, N-P
dc.contributor.authorLhuillier, C
dc.contributor.authorGruber, S
dc.contributor.authorChen, Q
dc.contributor.authorZhang, F
dc.contributor.authorZhou, XK
dc.contributor.authorGross, SS
dc.contributor.authorFormenti, SC
dc.contributor.authorDemaria, S
dc.date.accessioned2020-09-30T10:59:33Z
dc.date.issued2020-04
dc.identifier.citationCancer immunology research, 2020, 8 (4), pp. 465 - 478
dc.identifier.issn2326-6066
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4092
dc.identifier.eissn2326-6074
dc.identifier.doi10.1158/2326-6066.cir-19-0449
dc.description.abstractThe ability of focal radiotherapy to promote priming of tumor-specific CD8+ T cells and increase responses to immunotherapy is dependent on infiltration of the tumor by Batf3-dependent conventional dendritic cell type 1 (cDC1) cells. Such infiltration is driven by radiotherapy-induced IFN type I (IFN-I). Other signals may also modulate cDC1 infiltration of irradiated tumors. Here we found increased expression of adenosine-generating enzymes CD38 and CD73 in irradiated mouse and human breast cancer cells and increased adenosine in mouse tumors following radiotherapy. CD73 blockade alone had no effect. CD73 blockade with radiotherapy restored radiotherapy-induced cDC1 infiltration of tumors in settings where radiotherapy induction of IFN-I was suboptimal. In the absence of radiotherapy-induced IFN-I, blockade of CD73 was required for rejection of the irradiated tumor and for systemic tumor control (abscopal effect) in the context of cytotoxic T-lymphocyte-associated protein 4 blockade. These results suggest that CD73 may be a radiation-induced checkpoint, and that CD73 blockade in combination with radiotherapy and immune checkpoint blockade might improve patient response to therapy.
dc.formatPrint-Electronic
dc.format.extent465 - 478
dc.languageeng
dc.language.isoeng
dc.subjectDendritic Cells
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectMice, Knockout
dc.subjectHumans
dc.subjectMice
dc.subjectNeoplasms
dc.subject5'-Nucleotidase
dc.subjectInterferon Type I
dc.subjectAdenosine
dc.subjectFemale
dc.titleCD73 Blockade Promotes Dendritic Cell Infiltration of Irradiated Tumors and Tumor Rejection.
dc.typeJournal Article
dcterms.dateAccepted2020-02-04
rioxxterms.versionofrecord10.1158/2326-6066.cir-19-0449
rioxxterms.licenseref.startdate2020-04
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer immunology research
pubs.issue4
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/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radiation-enhanced Immunotherapy
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/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radiation-enhanced Immunotherapy
pubs.publication-statusPublished
pubs.volume8
pubs.embargo.termsNot known
icr.researchteamRadiation-enhanced Immunotherapyen_US
dc.contributor.icrauthorWennerberg, Eriken


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