dc.contributor.author | Annels, NE | |
dc.contributor.author | Simpson, GR | |
dc.contributor.author | Denyer, M | |
dc.contributor.author | Arif, M | |
dc.contributor.author | Coffey, M | |
dc.contributor.author | Melcher, A | |
dc.contributor.author | Harrington, K | |
dc.contributor.author | Vile, R | |
dc.contributor.author | Pandha, H | |
dc.date.accessioned | 2021-03-24T10:04:18Z | |
dc.date.available | 2021-03-24T10:04:18Z | |
dc.date.issued | 2021-03-26 | |
dc.identifier.citation | Molecular therapy oncolytics, 2021, 20 pp. 434 - 446 | |
dc.identifier.issn | 2372-7705 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4440 | |
dc.identifier.eissn | 2372-7705 | |
dc.identifier.doi | 10.1016/j.omto.2020.09.010 | |
dc.description.abstract | Prostate cancers are considered "cold" tumors characterized by minimal T cell infiltrates, absence of a type I interferon (IFN) signature, and the presence of immunosuppressive cells. This non-inflamed phenotype is likely responsible for the lack of sensitivity of prostate cancer patients to immune checkpoint blockade (ICB) therapy. Oncolytic virus therapy can potentially overcome this resistance to immunotherapy in prostate cancers by transforming cold tumors into "hot," immune cell-infiltrated tumors. We investigated whether the combination of intratumoral oncolytic reovirus, followed by targeted blockade of Programmed cell death protein 1 (PD-1) checkpoint inhibition and/or the immunomodulatory CD73/Adenosine system can enhance anti-tumor immunity. Treatment of subcutaneous TRAMP-C2 prostate tumors with combined intratumoral reovirus and anti-PD-1 or anti-CD73 antibody significantly enhanced survival of mice compared with reovirus or either antibody therapy alone. Only combination therapy led to rejection of pre-established tumors and protection from tumor re-challenge. This therapeutic effect was dependent on CD4+ T cells and natural killer (NK) cells. NanoString immune profiling of tumors confirmed that reovirus increased tumor immune cell infiltration and revealed an upregulation of the immune-regulatory receptor, B- and T-lymphocyte attenuator (BTLA). This expression of BTLA on innate antigen-presenting cells (APCs) and its ligand, Herpesvirus entry mediator (HVEM), on T cells from reovirus-infected tumors was in keeping with a role for the HVEM-BTLA pathway in promoting the potent anti-tumor memory response observed. | |
dc.format | Electronic-eCollection | |
dc.format.extent | 434 - 446 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Oncolytic Reovirus-Mediated Recruitment of Early Innate Immune Responses Reverses Immunotherapy Resistance in Prostate Tumors. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-09-30 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1016/j.omto.2020.09.010 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Molecular therapy oncolytics | |
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 | |
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.publication-status | Published | |
pubs.volume | 20 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Targeted Therapy | |
icr.researchteam | Targeted Therapy | |
dc.contributor.icrauthor | Melcher, Alan | |
dc.contributor.icrauthor | Harrington, Kevin | |