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Tumor-immune landscape patterns before and after chemoradiation in resectable esophageal adenocarcinomas
- Source :
- Journal of pathology, 256(3), 282-296. John Wiley and Sons Ltd, Soeratram, T T D, Creemers, A, Meijer, S L, de Boer, O J, Vos, W, Hooijer, G K J, van Berge Henegouwen, M I, Hulshof, M C C M, Bergman, J J G H M, Lei, M, Bijlsma, M F, Ylstra, B, van Grieken, N C T & van Laarhoven, H W M 2022, ' Tumor-immune landscape patterns before and after chemoradiation in resectable esophageal adenocarcinomas ', Journal of Pathology, vol. 256, no. 3, pp. 282-296 . https://doi.org/10.1002/path.5832, Journal of Pathology, 256(3), 282-296. John Wiley and Sons Ltd
- Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Male
PD-L1
medicine.medical_specialty
Time Factors
Databases, Factual
Esophageal Neoplasms
esophageal adenocarcinoma
medicine.medical_treatment
Adenocarcinoma
CD8-Positive T-Lymphocytes
Gastroenterology
Pathology and Forensic Medicine
chemoradiotherapy
Immune system
Lymphocytes, Tumor-Infiltrating
Internal medicine
medicine
Biomarkers, Tumor
Tumor Microenvironment
Humans
digital image analysis
Neoplasm Staging
Retrospective Studies
Tumor microenvironment
tumor-immune microenvironment
biology
Tumor-infiltrating lymphocytes
business.industry
FOXP3
treatment response
Immunotherapy
Chemoradiotherapy, Adjuvant
Middle Aged
Neoadjuvant Therapy
Esophagectomy
Treatment Outcome
tumor-infiltrating lymphocytes
immunohistochemistry
biology.protein
biomarker
Female
business
Chemoradiotherapy
CD8
Subjects
Details
- Language :
- English
- ISSN :
- 00223417
- Database :
- OpenAIRE
- Journal :
- Journal of pathology, 256(3), 282-296. John Wiley and Sons Ltd, Soeratram, T T D, Creemers, A, Meijer, S L, de Boer, O J, Vos, W, Hooijer, G K J, van Berge Henegouwen, M I, Hulshof, M C C M, Bergman, J J G H M, Lei, M, Bijlsma, M F, Ylstra, B, van Grieken, N C T & van Laarhoven, H W M 2022, ' Tumor-immune landscape patterns before and after chemoradiation in resectable esophageal adenocarcinomas ', Journal of Pathology, vol. 256, no. 3, pp. 282-296 . https://doi.org/10.1002/path.5832, Journal of Pathology, 256(3), 282-296. John Wiley and Sons Ltd
- Accession number :
- edsair.doi.dedup.....1856705863ef7601a17affce5b8f8225