The adaptive immune and immune checkpoint landscape of neoadjuvant treated esophageal adenocarcinoma using digital pathology quantitation.
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Date
2020-06-01ICR Author
Author
Humphries, MP
Craig, SG
Kacprzyk, R
Fisher, NC
Bingham, V
McQuaid, S
Murray, GI
McManus, D
Turkington, RC
James, J
Salto-Tellez, M
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Esophagus
Lymphocytes, Tumor-Infiltrating
Humans
Adenocarcinoma
Esophageal Neoplasms
Prognosis
Neoadjuvant Therapy
Esophagectomy
Tissue Array Analysis
Follow-Up Studies
Gene Expression Profiling
Middle Aged
Female
Male
Adaptive Immunity
Kaplan-Meier Estimate
Tumor Microenvironment
Biomarkers, Tumor
Immune Checkpoint Inhibitors
Research team
Integrated Pathology
Language
eng
Date accepted
2020-05-21
License start date
2020-06
Citation
BMC cancer, 2020, 20 (1), pp. 500 - ?
Publisher
BMC