dc.contributor.author | Humphries, MP | |
dc.contributor.author | Craig, SG | |
dc.contributor.author | Kacprzyk, R | |
dc.contributor.author | Fisher, NC | |
dc.contributor.author | Bingham, V | |
dc.contributor.author | McQuaid, S | |
dc.contributor.author | Murray, GI | |
dc.contributor.author | McManus, D | |
dc.contributor.author | Turkington, RC | |
dc.contributor.author | James, J | |
dc.contributor.author | Salto-Tellez, M | |
dc.date.accessioned | 2020-08-27T12:09:58Z | |
dc.date.issued | 2020-06-01 | |
dc.identifier.citation | BMC cancer, 2020, 20 (1), pp. 500 - ? | |
dc.identifier.issn | 1471-2407 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4039 | |
dc.identifier.eissn | 1471-2407 | |
dc.identifier.doi | 10.1186/s12885-020-06987-y | |
dc.description.abstract | BACKGROUND: 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.format | Electronic | |
dc.format.extent | 500 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BMC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Esophagus | |
dc.subject | Lymphocytes, Tumor-Infiltrating | |
dc.subject | Humans | |
dc.subject | Adenocarcinoma | |
dc.subject | Esophageal Neoplasms | |
dc.subject | Prognosis | |
dc.subject | Neoadjuvant Therapy | |
dc.subject | Esophagectomy | |
dc.subject | Tissue Array Analysis | |
dc.subject | Follow-Up Studies | |
dc.subject | Gene Expression Profiling | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Adaptive Immunity | |
dc.subject | Kaplan-Meier Estimate | |
dc.subject | Tumor Microenvironment | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Immune Checkpoint Inhibitors | |
dc.title | The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-05-21 | |
rioxxterms.versionofrecord | 10.1186/s12885-020-06987-y | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-06 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | BMC cancer | |
pubs.issue | 1 | |
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 | Published | |
pubs.volume | 20 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Integrated Pathology | |
dc.contributor.icrauthor | Salto-Tellez, Manuel | |