Show simple item record

dc.contributor.authorPennycuick, A
dc.contributor.authorTeixeira, VH
dc.contributor.authorAbdulJabbar, K
dc.contributor.authorRaza, SEA
dc.contributor.authorLund, T
dc.contributor.authorAkarca, AU
dc.contributor.authorRosenthal, R
dc.contributor.authorKalinke, L
dc.contributor.authorChandrasekharan, DP
dc.contributor.authorPipinikas, CP
dc.contributor.authorLee-Six, H
dc.contributor.authorHynds, RE
dc.contributor.authorGowers, KHC
dc.contributor.authorHenry, JY
dc.contributor.authorMillar, FR
dc.contributor.authorHagos, YB
dc.contributor.authorDenais, C
dc.contributor.authorFalzon, M
dc.contributor.authorMoore, DA
dc.contributor.authorAntoniou, S
dc.contributor.authorDurrenberger, PF
dc.contributor.authorFurness, AJ
dc.contributor.authorCarroll, B
dc.contributor.authorMarceaux, C
dc.contributor.authorAsselin-Labat, M-L
dc.contributor.authorLarson, W
dc.contributor.authorBetts, C
dc.contributor.authorCoussens, LM
dc.contributor.authorThakrar, RM
dc.contributor.authorGeorge, J
dc.contributor.authorSwanton, C
dc.contributor.authorThirlwell, C
dc.contributor.authorCampbell, PJ
dc.contributor.authorMarafioti, T
dc.contributor.authorYuan, Y
dc.contributor.authorQuezada, SA
dc.contributor.authorMcGranahan, N
dc.contributor.authorJanes, SM
dc.date.accessioned2020-10-27T15:53:40Z
dc.date.issued2020-07-20
dc.description.abstractBefore squamous cell lung cancer develops, precancerous lesions can be found in the airways. From longitudinal monitoring, we know that only half of such lesions become cancer, whereas a third spontaneously regress. Although recent studies have described the presence of an active immune response in high-grade lesions, the mechanisms underpinning clinical regression of precancerous lesions remain unknown. Here, we show that host immune surveillance is strongly implicated in lesion regression. Using bronchoscopic biopsies from human subjects, we find that regressive carcinoma in situ lesions harbor more infiltrating immune cells than those that progress to cancer. Moreover, molecular profiling of these lesions identifies potential immune escape mechanisms specifically in those that progress to cancer: antigen presentation is impaired by genomic and epigenetic changes, CCL27-CCR10 signaling is upregulated, and the immunomodulator TNFSF9 is downregulated. Changes appear intrinsic to the carcinoma in situ lesions, as the adjacent stroma of progressive and regressive lesions are transcriptomically similar. SIGNIFICANCE: Immune evasion is a hallmark of cancer. For the first time, this study identifies mechanisms by which precancerous lesions evade immune detection during the earliest stages of carcinogenesis and forms a basis for new therapeutic strategies that treat or prevent early-stage lung cancer.See related commentary by Krysan et al., p. 1442.This article is highlighted in the In This Issue feature, p. 1426.en_GB
dc.identifier.citationVol. 10, pp. 1489 - 1499en_GB
dc.identifier.doi10.1158/2159-8290.CD-19-1366
dc.identifier.other2159-8290.CD-19-1366
dc.identifier.urihttp://hdl.handle.net/10871/123391
dc.language.isoenen_GB
dc.publisherAmerican Association for Cancer Researchen_GB
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pubmed/32690541en_GB
dc.relation.urlhttps://www.ebi.ac.uk/ega/en_GB
dc.relation.urlhttps://idr.openmicroscopy.orgen_GB
dc.rights.embargoreasonUnder embargo until 20 July 2021 in compliance with publisher policyen_GB
dc.rights©2020 American Association for Cancer Researchen_GB
dc.titleImmune Surveillance in Clinical Regression of Preinvasive Squamous Cell Lung Canceren_GB
dc.typeArticleen_GB
dc.date.available2020-10-27T15:53:40Z
exeter.place-of-publicationUnited Statesen_GB
dc.descriptionThis is the author accepted manuscript. the final version is available from the American Association for Cancer Research via the DOI in this recorden_GB
dc.descriptionData Availability: All raw data used in this study is publicly available. Previously published CIS gene expression and methylation data is stored on GEO under accession number GSE108124; matched stromal gene expression data is stored under accession number GSE133690. Previously published CIS whole genome sequencing data is available from the European Genome Phenome Archive (https://www.ebi.ac.uk/ega/) under accession number EGAD00001003883. Annotated H&E images of all samples used for lymphocyte quantification were deposited to the Image Data Resource (https://idr.openmicroscopy.org) under accession number idr0082.en_GB
dc.descriptionCode Availability: All code used in our analysis will be made available at http://github.com/ucl446 respiratory/cis_immunology on publication. All software information, and parameters used in our analysis can be found here.en_GB
dc.identifier.journalCancer Discoveryen_GB
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_GB
dcterms.dateAccepted2020-07-14
rioxxterms.versionAMen_GB
rioxxterms.licenseref.startdate2020-07-20
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2020-10-27T15:51:12Z
refterms.versionFCDAM
refterms.panelAen_GB


Files in this item

This item appears in the following Collection(s)

Show simple item record