Tumor‐immune landscape patterns before and after chemoradiation in resectable esophageal adenocarcinomas

Immunotherapy is a new anti‐cancer treatment option, showing promising results in clinical trials. To investigate potential immune biomarkers in esophageal adenocarcinoma (EAC), we explored immune landscape patterns in the tumor microenvironment before and after neoadjuvant chemoradiation (nCRT). Se...

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Bibliographic Details
Published in:The Journal of pathology 2022-03, Vol.256 (3), p.282-296
Main Authors: Soeratram, Tanya TD, Creemers, Aafke, Meijer, Sybren L, Boer, Onno J, Vos, Wim, Hooijer, Gerrit KJ, Berge Henegouwen, Mark I, Hulshof, Maarten CCM, Bergman, Jacques JGHM, Lei, Ming, Bijlsma, Maarten F, Ylstra, Bauke, Grieken, Nicole CT, Laarhoven, Hanneke WM
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adenocarcinoma - chemistry
Adenocarcinoma - immunology
Adenocarcinoma - pathology
Adenocarcinoma - therapy
Apoptosis
biomarker
Biomarkers, Tumor - analysis
Biopsy
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell death
Chemoradiotherapy
Chemoradiotherapy, Adjuvant - adverse effects
Clinical trials
Cytokeratin
Databases, Factual
digital image analysis
Epithelium
esophageal adenocarcinoma
Esophageal cancer
Esophageal Neoplasms - chemistry
Esophageal Neoplasms - immunology
Esophageal Neoplasms - pathology
Esophageal Neoplasms - therapy
Esophagectomy - adverse effects
Esophagus
Female
Forkhead protein
Foxp3 protein
Humans
immunohistochemistry
Immunotherapy
Inflammation
Invasiveness
Lymphocytes, Tumor-Infiltrating - immunology
Major histocompatibility complex
Male
Middle Aged
Neoadjuvant Therapy - adverse effects
Neoplasm Staging
Original
Patients
PD-1 protein
PD-L1 protein
PD‐L1
Retrospective Studies
Stroma
Time Factors
Treatment Outcome
treatment response
Tumor microenvironment
Tumor Microenvironment - immunology
Tumors
tumor‐immune microenvironment
tumor‐infiltrating lymphocytes
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Summary:Immunotherapy is a new anti‐cancer treatment option, showing promising results in clinical trials. To investigate potential immune biomarkers in esophageal adenocarcinoma (EAC), we explored immune landscape patterns in the tumor microenvironment before and after neoadjuvant chemoradiation (nCRT). Sections from matched pretreatment biopsies and post‐nCRT resection specimens (n = 188) were stained for (1) programmed death‐ligand 1 (PD‐L1, CD274); (2) programmed cell death protein 1 (PD‐1, CD279), forkhead box P3 (FOXP3), CD8, pan‐cytokeratin multiplex; and (3) an MHC class I, II duplex. The densities of tumor‐associated immune cells (TAICs) were calculated using digital image analyses and correlated to histopathological nCRT response [tumor regression grade (TRG)], survival, and post‐nCRT immune patterns. PD‐L1 positivity defined by a combined positive score of >1 was associated with a better response post‐nCRT (TRG 1–3 versus 4, 5, p = 0.010). In addition, high combined mean densities of CD8+, FOXP3+, and PD‐1+ TAICs in the tumor epithelium and stroma of biopsies were associated with a better response (TRG 1–3 versus 4, 5, p = 0.025 and p = 0.044, respectively). Heterogeneous TAIC density patterns were observed post‐nCRT, with significantly higher CD8+ and PD‐1+ TAIC mean densities compared with biopsies (both p = 0.000). Three immune landscape patterns were defined post‐nCRT: ‘inflamed’, ‘invasive margin’, and ‘desert’, of which ‘inflamed’ was the most frequent (57%). Compared with matched biopsies, resection specimens with ‘inflamed’ tumors showed a significantly higher increase in CD8+ density compared with non‐inflamed tumors post‐nCRT (p = 0.000). In this cohort of EAC patients, higher TAIC densities in pretreatment biopsies were associated with response to nCRT. This warrants future research into the potential of the tumor‐immune landscape for patient stratification and novel (immune) therapeutic strategies. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd on behalf of The Pathological Society of Great Britain and Ireland.
ISSN:0022-3417
1096-9896
DOI:10.1002/path.5832