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Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus

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Title: Distribution of tumor-infiltrating-T-lymphocytes and possible tumor-escape mechanisms avoiding immune cell attack in locally advanced adenocarcinomas of the esophagus
Authors: M. Schoemmel, H. Loeser, M. Kraemer, S. Wagener-Ryczek, A. Hillmer, C. Bruns, M. Thelen, W. Schröder, T. Zander, A. Lechner, R. Buettner, H. Schlösser, F. Gebauer, A. Quaas
Source: Clin Transl Oncol
Publisher Information: Springer Science and Business Media LLC, 2021.
Publication Year: 2021
Subject Terms: Male, 0301 basic medicine, Time Factors, Esophageal Neoplasms, Down-Regulation, Adenocarcinoma, B7-H1 Antigen, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, HLA-B Antigens/metabolism [MeSH], Tumor Escape/immunology [MeSH], PD-L1, Aged [MeSH], Esophageal Neoplasms/immunology [MeSH], Esophageal Neoplasms/pathology [MeSH], Tumor Microenvironment/immunology [MeSH], B7-H1 Antigen/metabolism [MeSH], Male [MeSH], Adenocarcinoma of the esophagus, Adenocarcinoma/pathology [MeSH], Adenocarcinoma/immunology [MeSH], Research Article, Neoplasm Invasiveness/immunology [MeSH], HLA-A Antigens/metabolism [MeSH], Inflammation/immunology [MeSH], Female [MeSH], MHC1, Down-Regulation [MeSH], B7-H1 Antigen/analysis [MeSH], Immunity, Cellular [MeSH], Lymphocyte Count [MeSH], Humans [MeSH], Inflammation, Middle Aged [MeSH], Time Factors [MeSH], HLA-B Antigens/analysis [MeSH], Computer applications software, Prognosis [MeSH], Esophageal Neoplasms/mortality [MeSH], Adenocarcinoma/mortality [MeSH], Lymphocytes, Tumor-Infiltrating/cytology [MeSH], HLA-A Antigens/analysis [MeSH], Tumor Microenvironment, Humans, Neoplasm Invasiveness, Lymphocyte Count, Aged, Immunity, Cellular, HLA-A Antigens, Middle Aged, Prognosis, 3. Good health, HLA-B Antigens, Female, Tumor Escape
Description: Introduction The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack. Patients and methods We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data. Results Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages. Discussion Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.
Document Type: Article
Other literature type
Language: English
ISSN: 1699-3055
1699-048X
DOI: 10.1007/s12094-021-02556-2
Access URL: https://link.springer.com/content/pdf/10.1007/s12094-021-02556-2.pdf
https://pubmed.ncbi.nlm.nih.gov/33566304
https://link.springer.com/content/pdf/10.1007/s12094-021-02556-2.pdf
https://dialnet.unirioja.es/servlet/articulo?codigo=7997280
https://europepmc.org/article/MED/33566304
https://link.springer.com/article/10.1007/s12094-021-02556-2
https://pubmed.ncbi.nlm.nih.gov/33566304/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238763/
https://repository.publisso.de/resource/frl:6445604
Rights: CC BY
URL: http://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) .
Accession Number: edsair.doi.dedup.....a348f59f4c64d83e8ba59d7b7600b1eb
Database: OpenAIRE
Description
Abstract:Introduction The inflammatory microenvironment has emerged as one of the focuses of cancer research. Little is known about the immune environment in esophageal adenocarcinoma (EAC) and possible tumor-escape mechanisms to avoid immune cell attack. Patients and methods We measured T cell inflammation (CD3, CD8) in the microenvironment using a standardized software-based evaluation algorithm considering different predefined tumor areas as well as expression of MHC class 1 and PD-L1 on 75 analyzable primarily resected and locally advanced (≥ pT2) EACs. We correlated these findings statistically with clinical data. Results Patients with high amounts of T cell infiltration in their tumor center showed a significant survival benefit of 41.4 months compared to 16.3 months in T cell poor tumors (p = 0.025), although CD3 fails to serve as an independent prognostic marker in multivariate analysis. For the invasion zone, a correlation between number of T-cells and overall survival was not detectable. Loss of MHC1 protein expression on tumor cells was seen in 32% and PD-L1 expression using the combined positive score (CPS) in 21.2%. Most likely due to small numbers of cases, both markers are not prognostically relevant, even though PD-L1 expression correlates with advanced tumor stages. Discussion Our analyses reveal an outstanding, though not statistically independent, prognostic relevance of T-cell-rich inflammation in our group of EACs, in particular driven by the tumor center. For the first time, we describe that the inner part of the invasion zone in EACs shows significantly fewer T-cells than other tumor segments and is prognostically irrelevant. We also demonstrate that the loss of antigen presenting ability via MHC1 downregulation by the carcinoma cells is a common escape mechanism in EACs. Future work will need to show whether tumors with MHC class 1 loss respond less well to immunotherapy.
ISSN:16993055
1699048X
DOI:10.1007/s12094-021-02556-2