The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation
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 discov...
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doaj-835b6b88f74b4c999fdf8a0998cc6c0a2020-11-25T03:31:23ZengBMCBMC Cancer1471-24072020-06-0120111110.1186/s12885-020-06987-yThe adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitationMatthew P. Humphries0Stephanie G. Craig1Rafal Kacprzyk2Natalie C. Fisher3Victoria Bingham4Stephen McQuaid5Graeme I. Murray6Damian McManus7Richard C. Turkington8Jacqueline James9Manuel Salto-Tellez10Precision Medicine Centre of Excellence, Patrick G Johnston Centre for Cancer Research, Queen’s UniversityPrecision Medicine Centre of Excellence, Patrick G Johnston Centre for Cancer Research, Queen’s UniversityPrecision Medicine Centre of Excellence, Patrick G Johnston Centre for Cancer Research, Queen’s UniversityPrecision Medicine Centre of Excellence, Patrick G Johnston Centre for Cancer Research, Queen’s UniversityPrecision Medicine Centre of Excellence, Patrick G Johnston Centre for Cancer Research, Queen’s UniversityPrecision Medicine Centre of Excellence, Patrick G Johnston Centre for Cancer Research, Queen’s UniversityPathology, School of Medicine, Medical Sciences and Nutrition, University of AberdeenCellular Pathology, Belfast Health and Social Care Trust, Belfast City HospitalPatrick G Johnston Centre for Cancer Research, Queen’s UniversityPrecision Medicine Centre of Excellence, Patrick G Johnston Centre for Cancer Research, Queen’s UniversityPrecision Medicine Centre of Excellence, Patrick G Johnston Centre for Cancer Research, Queen’s UniversityAbstract 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.http://link.springer.com/article/10.1186/s12885-020-06987-yEsophageal adenocarcinomaImmune checkpointMultiplex IHCImage analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthew P. Humphries Stephanie G. Craig Rafal Kacprzyk Natalie C. Fisher Victoria Bingham Stephen McQuaid Graeme I. Murray Damian McManus Richard C. Turkington Jacqueline James Manuel Salto-Tellez |
spellingShingle |
Matthew P. Humphries Stephanie G. Craig Rafal Kacprzyk Natalie C. Fisher Victoria Bingham Stephen McQuaid Graeme I. Murray Damian McManus Richard C. Turkington Jacqueline James Manuel Salto-Tellez The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation BMC Cancer Esophageal adenocarcinoma Immune checkpoint Multiplex IHC Image analysis |
author_facet |
Matthew P. Humphries Stephanie G. Craig Rafal Kacprzyk Natalie C. Fisher Victoria Bingham Stephen McQuaid Graeme I. Murray Damian McManus Richard C. Turkington Jacqueline James Manuel Salto-Tellez |
author_sort |
Matthew P. Humphries |
title |
The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation |
title_short |
The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation |
title_full |
The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation |
title_fullStr |
The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation |
title_full_unstemmed |
The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation |
title_sort |
adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2020-06-01 |
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. |
topic |
Esophageal adenocarcinoma Immune checkpoint Multiplex IHC Image analysis |
url |
http://link.springer.com/article/10.1186/s12885-020-06987-y |
work_keys_str_mv |
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