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The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation

Authors
  • Humphries, Matthew P.1
  • Craig, Stephanie G.1
  • Kacprzyk, Rafal1
  • Fisher, Natalie C.1
  • Bingham, Victoria1
  • McQuaid, Stephen1, 2, 1
  • Murray, Graeme I.3
  • McManus, Damian2
  • Turkington, Richard C.1
  • James, Jacqueline1, 2, 1
  • Salto-Tellez, Manuel1, 2
  • 1 Queen’s University, Belfast, UK , Belfast (United Kingdom)
  • 2 Belfast City Hospital, Lisburn Road, Belfast, UK , Belfast (United Kingdom)
  • 3 University of Aberdeen, Aberdeen, Scotland , Aberdeen (United Kingdom)
Type
Published Article
Journal
BMC Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jun 01, 2020
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12885-020-06987-y
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundLimited studies examine the immune landscape in Esophageal Adenocarcinoma (EAC). We aim to identify novel associations, which may inform immunotherapy treatment stratification.MethodsThree 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.ResultsCD3, 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.ConclusionsMultiplexing 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.

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