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J Pathol. 2021 Nov 07; doi: 10.1002/path.5832. Epub 2021 Nov 07.

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

The Journal of pathology

Tanya Td Soeratram, Aafke Creemers, Sybren L Meijer, Onno J de Boer, Wim Vos, Gerrit Kj Hooijer, Mark I van Berge Henegouwen, Maarten Ccm Hulshof, Jacques Jghm Bergman, Ming Lei, Maarten F Bijlsma, Bauke Ylstra, Nicole Ct van Grieken, Hanneke Wm van Laarhoven


  1. Department of Pathology, Amsterdam UMC, VU University, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  2. Laboratory of Experimental Oncology and Radiobiology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  3. Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  4. Department of Pathology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  5. Department of Surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  6. Department of Radiotherapy, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  7. Department of Gastroenterology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands.
  8. Bristol-Myers Squibb, Princeton, NJ, USA.

PMID: 34743329 DOI: 10.1002/path.5832


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

© 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Keywords: PD-L1; biomarker; chemoradiotherapy; digital image analysis; esophageal adenocarcinoma; immunohistochemistry; treatment response; tumor-immune microenvironment; tumor-infiltrating lymphocytes


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