dc.contributor.author | Alderdice, M | |
dc.contributor.author | Craig, SG | |
dc.contributor.author | Humphries, MP | |
dc.contributor.author | Gilmore, A | |
dc.contributor.author | Johnston, N | |
dc.contributor.author | Bingham, V | |
dc.contributor.author | Coyle, V | |
dc.contributor.author | Senevirathne, S | |
dc.contributor.author | Longley, DB | |
dc.contributor.author | Loughrey, MB | |
dc.contributor.author | McQuaid, S | |
dc.contributor.author | James, JA | |
dc.contributor.author | Salto-Tellez, M | |
dc.contributor.author | Lawler, M | |
dc.contributor.author | McArt, DG | |
dc.date.accessioned | 2021-05-24T08:21:09Z | |
dc.date.available | 2021-05-24T08:21:09Z | |
dc.date.issued | 2021-04-09 | |
dc.identifier.citation | NAR genomics and bioinformatics, 2021, 3 (2), pp. lqab016 - ? | |
dc.identifier.issn | 2631-9268 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4573 | |
dc.identifier.eissn | 2631-9268 | |
dc.identifier.doi | 10.1093/nargab/lqab016 | |
dc.description.abstract | Identifying robust predictive biomarkers to stratify colorectal cancer (CRC) patients based on their response to immune-checkpoint therapy is an area of unmet clinical need. Our evolutionary algorithm Atlas Correlation Explorer (ACE) represents a novel approach for mining The Cancer Genome Atlas (TCGA) data for clinically relevant associations. We deployed ACE to identify candidate predictive biomarkers of response to immune-checkpoint therapy in CRC. We interrogated the colon adenocarcinoma (COAD) gene expression data across nine immune-checkpoints (PDL1, PDCD1, CTLA4, LAG3, TIM3, TIGIT, ICOS, IDO1 and BTLA). IL2RB was identified as the most common gene associated with immune-checkpoint genes in CRC. Using human/murine single-cell RNA-seq data, we demonstrated that IL2RB was expressed predominantly in a subset of T-cells associated with increased immune-checkpoint expression (P < 0.0001). Confirmatory IL2RB immunohistochemistry (IHC) analysis in a large MSI-H colon cancer tissue microarray (TMA; n = 115) revealed sensitive, specific staining of a subset of lymphocytes and a strong association with FOXP3+ lymphocytes (P < 0.0001). IL2RB mRNA positively correlated with three previously-published gene signatures of response to immune-checkpoint therapy (P < 0.0001). Our evolutionary algorithm has identified IL2RB to be extensively linked to immune-checkpoints in CRC; its expression should be investigated for clinical utility as a potential predictive biomarker for CRC patients receiving immune-checkpoint blockade. | |
dc.format | Electronic-eCollection | |
dc.format.extent | lqab016 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | OXFORD UNIV PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Evolutionary genetic algorithm identifies IL2RB as a potential predictive biomarker for immune-checkpoint therapy in colorectal cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-03-26 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1093/nargab/lqab016 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | NAR genomics and bioinformatics | |
pubs.issue | 2 | |
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/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology | |
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/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Integrated Pathology | |
pubs.publication-status | Accepted | |
pubs.volume | 3 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Integrated Pathology | |
icr.researchteam | Integrated Pathology | |
dc.contributor.icrauthor | Salto-Tellez, Manuel | |