dc.contributor.author | Litchfield, K | |
dc.contributor.author | Reading, JL | |
dc.contributor.author | Lim, EL | |
dc.contributor.author | Xu, H | |
dc.contributor.author | Liu, P | |
dc.contributor.author | Al-Bakir, M | |
dc.contributor.author | Wong, YNS | |
dc.contributor.author | Rowan, A | |
dc.contributor.author | Funt, SA | |
dc.contributor.author | Merghoub, T | |
dc.contributor.author | Perkins, D | |
dc.contributor.author | Lauss, M | |
dc.contributor.author | Svane, IM | |
dc.contributor.author | Jönsson, G | |
dc.contributor.author | Herrero, J | |
dc.contributor.author | Larkin, J | |
dc.contributor.author | Quezada, SA | |
dc.contributor.author | Hellmann, MD | |
dc.contributor.author | Turajlic, S | |
dc.contributor.author | Swanton, C | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2022-08-30T08:49:16Z | |
dc.date.available | 2022-08-30T08:49:16Z | |
dc.date.issued | 2020-07-30 | |
dc.identifier | ARTN 3800 | |
dc.identifier | 10.1038/s41467-020-17526-5 | |
dc.identifier.citation | Nature Communications, 2020, 11 (1), pp. 3800 - | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5336 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-020-17526-5 | |
dc.description.abstract | Frameshift insertion/deletions (fs-indels) are an infrequent but highly immunogenic mutation subtype. Although fs-indels are degraded through the nonsense-mediated decay (NMD) pathway, we hypothesise that some fs-indels escape degradation and elicit anti-tumor immune responses. Using allele-specific expression analysis, expressed fs-indels are enriched in genomic positions predicted to escape NMD, and associated with higher protein expression, consistent with degradation escape (NMD-escape). Across four independent melanoma cohorts, NMD-escape mutations are significantly associated with clinical-benefit to checkpoint inhibitor (CPI) therapy (Pmeta = 0.0039). NMD-escape mutations are additionally found to associate with clinical-benefit in the low-TMB setting. Furthermore, in an adoptive cell therapy treated melanoma cohort, NMD-escape mutation count is the most significant biomarker associated with clinical-benefit. Analysis of functional T cell reactivity screens from personalized vaccine studies shows direct evidence of fs-indel derived neoantigens eliciting immune response, particularly those with highly elongated neo open reading frames. NMD-escape fs-indels represent an attractive target for biomarker optimisation and immunotherapy design. | |
dc.format | Electronic | |
dc.format.extent | 3800 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.relation.ispartof | Nature Communications | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Adoptive Transfer | |
dc.subject | Antigens, Neoplasm | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Frameshift Mutation | |
dc.subject | Humans | |
dc.subject | INDEL Mutation | |
dc.subject | Immunotherapy, Adoptive | |
dc.subject | Melanoma | |
dc.subject | Nonsense Mediated mRNA Decay | |
dc.subject | T-Lymphocytes | |
dc.subject | Tumor Escape | |
dc.subject | Whole Exome Sequencing | |
dc.title | Escape from nonsense-mediated decay associates with anti-tumor immunogenicity. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-06-30 | |
dc.date.updated | 2022-08-30T08:46:20Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41467-020-17526-5 | |
rioxxterms.licenseref.startdate | 2020-07-30 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/32733040 | |
pubs.issue | 1 | |
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/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.) | |
pubs.publication-status | Published online | |
pubs.volume | 11 | |
dc.contributor.icrauthor | Larkin, James | |
dc.contributor.icrauthor | Turajlic, Samra | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof James Larkin) on 2022-08-30. Deposit type is initial. No. of files: 1. Files: Escape from nonsense-mediated decay associates with anti-tumor immunogenicity.pdf | |