Affordable Access

Access to the full text

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

  • 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)
Published Article
BMC Cancer
Springer (Biomed Central Ltd.)
Publication Date
Jun 01, 2020
DOI: 10.1186/s12885-020-06987-y
Springer Nature


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.

Report this publication


Seen <100 times