Wagener-Ryczek, Svenja, Schoemmel, Max, Kraemer, Max, Bruns, Christiane, Schroeder, Wolfgang, Zander, Thomas, Gebauer, Florian, Alakus, Hakan, Merkelbach-Bruse, Sabine, Buettner, Reinhard, Loeser, Heike, Thelen, Martin ORCID: 0000-0002-2785-9726, Schlosser, Hans A. and Quaas, Alexander (2020). Immune profile and immunosurveillance in treatment-naive and neoadjuvantly treated esophageal adenocarcinoma. Cancer Immunol. Immunother., 69 (4). S. 523 - 534. NEW YORK: SPRINGER. ISSN 1432-0851

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Abstract

The outcome in esophageal adenocarcinoma (EAC) is still poor with only 20% of patients in Western populations surviving for more than 5 years. Almost nothing is known about the precise composition of immune cells and their gene expression profiles in primary resected EACs and also nothing compared to neoadjuvant treated EACs. This study analyzes and compares immune profiles of primary resected and neoadjuvant treated esophageal adenocarcinoma and unravels possible targets for immunotherapy. We analyzed 47 EAC in total considering a set of 30 primary treatment-naive EACs and 17 neoadjuvant pretreated (12 x CROSS, 5 x FLOT) using the Nanostring's panel-based gene expression platform including 770 genes being important in malignant tumors and their immune micromileu. Most of the significantly altered genes are involved in the regulation of immune responses, T-and B cell functions as well as antigen processing. Chemokine-receptor axes like the CXCL9, -10,-11/CXCR3- are prominent in esophageal adenocarcinoma with a fold change of up to 9.5 promoting cancer cell proliferation and metastasis. ARG1, as a regulator of T-cell fate is sixfold down-regulated in untreated primary esophageal tumors. The influence of the currently used neoadjuvant treatment revealed a down-regulation of nearly all important checkpoint markers and inflammatory related genes in the local microenvironment. We found a higher expression of checkpoint markers like LAG3, TIM3, CTLA4 and CD276 in comparison to PD-L1/PD-1 supporting clinical trials analyzing the efficacy of a combination of different checkpoint inhibitors in EACs. We found an up-regulation of CD38 or LILRB1 as examples of additional immune escape mechanism.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wagener-Ryczek, SvenjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoemmel, MaxUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kraemer, MaxUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruns, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeder, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gebauer, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alakus, HakanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merkelbach-Bruse, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loeser, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thelen, MartinUNSPECIFIEDorcid.org/0000-0002-2785-9726UNSPECIFIED
Schlosser, Hans A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Quaas, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-339347
DOI: 10.1007/s00262-019-02475-w
Journal or Publication Title: Cancer Immunol. Immunother.
Volume: 69
Number: 4
Page Range: S. 523 - 534
Date: 2020
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-0851
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CANCER SURVIVAL; ANTIGEN LOSS; CLASS-I; IMMUNOTHERAPY; NIVOLUMAB; ESCAPE; TARGET; TIM-3; PD-1Multiple languages
Oncology; ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33934

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