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dc.contributor.authorHumphries, MP
dc.contributor.authorCraig, SG
dc.contributor.authorKacprzyk, R
dc.contributor.authorFisher, NC
dc.contributor.authorBingham, V
dc.contributor.authorMcQuaid, S
dc.contributor.authorMurray, GI
dc.contributor.authorMcManus, D
dc.contributor.authorTurkington, RC
dc.contributor.authorJames, J
dc.contributor.authorSalto-Tellez, M
dc.date.accessioned2020-08-27T12:09:58Z
dc.date.issued2020-06
dc.identifier.citationBMC cancer, 2020, 20 (1), pp. 500 - ?
dc.identifier.issn1471-2407
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4039
dc.identifier.eissn1471-2407
dc.identifier.doi10.1186/s12885-020-06987-y
dc.description.abstractBackground Limited studies examine the immune landscape in Esophageal Adenocarcinoma (EAC). We aim to identify novel associations, which may inform immunotherapy treatment stratification.Methods Three hundred twenty-nine EAC cases were available in Tissue Microarrays (TMA) format. A discovery cohort of 166 EAC cases were stained immunohistochemically for range of adaptive immune (CD3, CD4, CD8 and CD45RO) and immune checkpoint biomarkers (ICOS, IDO-1, PD-L1, PD-1). A validation cohort of 163 EAC cases was also accessed. A digital pathology analysis approach was used to quantify biomarker density.Results CD3, CD4, CD8, CD45RO, ICOS and PD-1 were individually predictive of better overall survival (OS) (Log rank p = < 0.001; p = 0.014; p = 0.001; p = < 0.001; p = 0.008 and p = 0.026 respectively). Correlation and multivariate analysis identified high CD45RO/ICOS patients with significantly improved OS which was independently prognostic (HR = 0.445, (0.223-0.886), p = 0.021). Assessment of CD45RO and ICOS high cases in the validation cohort revealed an associated with improved OS (HR = 0.601 (0.363-0.996), p = 0.048). Multiplex IHC identified cellular co-expression of high CD45RO/ICOS. High CD45RO/ICOS patients have significantly improved OS.Conclusions Multiplexing identifies true cellular co-expression. These data demonstrate that co-expression of immune biomarkers are associated with better outcome in EAC and may provide evidence for immunotherapy treatment stratification.
dc.formatElectronic
dc.format.extent500 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectEsophagus
dc.subjectLymphocytes, Tumor-Infiltrating
dc.subjectHumans
dc.subjectAdenocarcinoma
dc.subjectEsophageal Neoplasms
dc.subjectPrognosis
dc.subjectNeoadjuvant Therapy
dc.subjectEsophagectomy
dc.subjectTissue Array Analysis
dc.subjectFollow-Up Studies
dc.subjectGene Expression Profiling
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectAdaptive Immunity
dc.subjectKaplan-Meier Estimate
dc.subjectTumor Microenvironment
dc.subjectBiomarkers, Tumor
dc.subjectImmune Checkpoint Inhibitors
dc.titleThe adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation.
dc.typeJournal Article
dcterms.dateAccepted2020-05-21
rioxxterms.versionofrecord10.1186/s12885-020-06987-y
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBMC cancer
pubs.issue1
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/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-statusPublished
pubs.volume20
pubs.embargo.termsNot known
icr.researchteamIntegrated Pathologyen_US
dc.contributor.icrauthorSalto-Tellez, Manuelen


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