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Anti-inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival

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Názov: Anti-inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival
Autori: Penelope Pelczar, Anastasios D. Giannou, Nicola Gagliani, Eric Freiwald, Thomas Roesch, Samuel Huber, Ansgar W. Lohse, Maximilian Bockhorn, Leonie Konczalla, Michael Tachezy, Oliver Mann, Stefan Steurer, Daniel Perez, Matthias Reeh, Karl-Frederick Karstens, Jakob R. Izbicki, Anna Woestemeier, Babett Steglich, Jan Kempski
Zdroj: Cancer Immunol Immunother
Informácie o vydavateľovi: Springer Science and Business Media LLC, 2020.
Rok vydania: 2020
Predmety: Male, 0301 basic medicine, 0303 health sciences, Esophageal Neoplasms, Anti-Inflammatory Agents, Adenocarcinoma, Survival Analysis, 3. Good health, Female [MeSH], Humans [MeSH], Survival Analysis [MeSH], Retrospective Studies [MeSH], Original Article, Anti-Inflammatory Agents/pharmacology [MeSH], Survival, Male [MeSH], Anti-Inflammatory Agents/therapeutic use [MeSH], Esophageal Neoplasms/mortality [MeSH], Esophageal Neoplasms/physiopathology [MeSH], Esophageal adenocarcinoma, Barrett's esophagus, Adenocarcinoma/mortality [MeSH], Anti-inflammatory environment, Adenocarcinoma/physiopathology [MeSH], Tumor Microenvironment [MeSH], 03 medical and health sciences, Tumor Microenvironment, Humans, Female, Retrospective Studies
Popis: Objective Reflux promotes esophageal adenocarcinomas (EACs) creating a chronic inflammatory environment. Survival rates are low due to early local recurrences and distant metastasis. Hence, there is a need for new potential treatment options like immunotherapies. However, the inflammatory microenvironment in EACs and its impact on patient outcome remain to be fully understood. Methods mRNA expression levels of pro- and anti-inflammatory markers in 39 EAC patients without neoadjuvant radio-chemotherapy were measured. Data were confirmed using flow cytometric analysis of freshly resected surgical specimens. Inflammatory alterations in premalignant lesions of Barrett’s esophagus were analyzed by immunohistochemistry. Results Expression levels of IL22 were reduced in EAC, while expression levels of FOXP3, IL10 and CTLA4 were increased. Flow cytometry demonstrated a strong infiltration of CD4+ T cells with a reduction in CD4+ T cells producing IL-22 or IL-17A. We also observed an increase in CD4+CD127lowFOXP3+ cells producing IL-10. Accumulation of FOXP3+ T cells occurred prior to malignant changes. High expression of IL10 and low expression of IL22 in EAC were associated with reduced overall survival. Moreover, increased expression of IL10, CTLA4 and PD1 in the unaltered esophageal mucosa distant to the EAC was also linked with an unfavorable prognosis. Conclusion EAC shows an anti-inflammatory environment, which strongly affects patient survival. The microscopically unaltered peritumoral tissue shows a similar anti-inflammatory pattern indicating an immunological field effect, which might contribute to early local recurrences despite radical resection. These data suggest that using checkpoint inhibitors targeting anti-inflammatory T cells would be a promising therapeutic strategy in EAC.
Druh dokumentu: Article
Other literature type
Jazyk: English
ISSN: 1432-0851
0340-7004
DOI: 10.1007/s00262-020-02517-8
Prístupová URL adresa: https://link.springer.com/content/pdf/10.1007/s00262-020-02517-8.pdf
https://pubmed.ncbi.nlm.nih.gov/32100077
https://link.springer.com/content/pdf/10.1007/s00262-020-02517-8.pdf
https://europepmc.org/article/PMC/PMC7230052
https://fis-uke.de/portal/de/publications/antiinflammatory-microenvironment-of-esophageal-adenocarcinomas-negatively-impacts-survival(a8653de8-ba8c-4495-b254-667766ba599a).html
https://pubmed.ncbi.nlm.nih.gov/32100077/
https://www.ncbi.nlm.nih.gov/pubmed/32100077
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230052
https://repository.publisso.de/resource/frl:6470322
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/) .
Prístupové číslo: edsair.doi.dedup.....5793f1e96beda472f8f0bfc6bae64224
Databáza: OpenAIRE
Popis
Abstrakt:Objective Reflux promotes esophageal adenocarcinomas (EACs) creating a chronic inflammatory environment. Survival rates are low due to early local recurrences and distant metastasis. Hence, there is a need for new potential treatment options like immunotherapies. However, the inflammatory microenvironment in EACs and its impact on patient outcome remain to be fully understood. Methods mRNA expression levels of pro- and anti-inflammatory markers in 39 EAC patients without neoadjuvant radio-chemotherapy were measured. Data were confirmed using flow cytometric analysis of freshly resected surgical specimens. Inflammatory alterations in premalignant lesions of Barrett’s esophagus were analyzed by immunohistochemistry. Results Expression levels of IL22 were reduced in EAC, while expression levels of FOXP3, IL10 and CTLA4 were increased. Flow cytometry demonstrated a strong infiltration of CD4+ T cells with a reduction in CD4+ T cells producing IL-22 or IL-17A. We also observed an increase in CD4+CD127lowFOXP3+ cells producing IL-10. Accumulation of FOXP3+ T cells occurred prior to malignant changes. High expression of IL10 and low expression of IL22 in EAC were associated with reduced overall survival. Moreover, increased expression of IL10, CTLA4 and PD1 in the unaltered esophageal mucosa distant to the EAC was also linked with an unfavorable prognosis. Conclusion EAC shows an anti-inflammatory environment, which strongly affects patient survival. The microscopically unaltered peritumoral tissue shows a similar anti-inflammatory pattern indicating an immunological field effect, which might contribute to early local recurrences despite radical resection. These data suggest that using checkpoint inhibitors targeting anti-inflammatory T cells would be a promising therapeutic strategy in EAC.
ISSN:14320851
03407004
DOI:10.1007/s00262-020-02517-8