Cargando…
Human lung carcinomas synthesize immunoregulatory glucocorticoids
The need for new options in lung cancer treatment inevitably leads back to basic research. The tumor itself and the tumor environment especially the interaction with the immune system need to be better understood to develop targeted therapies. In the context of lung cancer glucocorticoids (GC) are m...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935384/ https://www.ncbi.nlm.nih.gov/pubmed/36653475 http://dx.doi.org/10.1038/s41435-023-00194-y |
_version_ | 1784890017656602624 |
---|---|
author | Merk, Verena M. Grob, Leonie Fleischmann, Achim Brunner, Thomas |
author_facet | Merk, Verena M. Grob, Leonie Fleischmann, Achim Brunner, Thomas |
author_sort | Merk, Verena M. |
collection | PubMed |
description | The need for new options in lung cancer treatment inevitably leads back to basic research. The tumor itself and the tumor environment especially the interaction with the immune system need to be better understood to develop targeted therapies. In the context of lung cancer glucocorticoids (GC) are mainly known as a combination drug to attenuate side-effects of chemotherapies. However, endogenous extra-adrenal GC have been shown to substantially regulate local immune responses within various tissues, including the lung. In this study we investigated whether primary lung tumors have maintained the capacity to synthesize GC and may thereby regulate anti-tumor immune responses. We show that several non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) cell lines express key steroidogenic enzymes and synthesize bioactive GC under steady state conditions. We also show that tumor-derived GC can inhibit splenic T cell activation, thus demonstrating their immunoregulatory potential. Moreover, steroidogenic enzymes were detected by quantitative RT-PCR and immunohistochemistry in tissue sections of different human lung tumors, further strengthening the idea that human lung carcinomas regulate their microenvironment by releasing immunoregulatory GC, which potentially contributes to immune evasion and treatment resistance. |
format | Online Article Text |
id | pubmed-9935384 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-99353842023-02-18 Human lung carcinomas synthesize immunoregulatory glucocorticoids Merk, Verena M. Grob, Leonie Fleischmann, Achim Brunner, Thomas Genes Immun Brief Communication The need for new options in lung cancer treatment inevitably leads back to basic research. The tumor itself and the tumor environment especially the interaction with the immune system need to be better understood to develop targeted therapies. In the context of lung cancer glucocorticoids (GC) are mainly known as a combination drug to attenuate side-effects of chemotherapies. However, endogenous extra-adrenal GC have been shown to substantially regulate local immune responses within various tissues, including the lung. In this study we investigated whether primary lung tumors have maintained the capacity to synthesize GC and may thereby regulate anti-tumor immune responses. We show that several non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) cell lines express key steroidogenic enzymes and synthesize bioactive GC under steady state conditions. We also show that tumor-derived GC can inhibit splenic T cell activation, thus demonstrating their immunoregulatory potential. Moreover, steroidogenic enzymes were detected by quantitative RT-PCR and immunohistochemistry in tissue sections of different human lung tumors, further strengthening the idea that human lung carcinomas regulate their microenvironment by releasing immunoregulatory GC, which potentially contributes to immune evasion and treatment resistance. Nature Publishing Group UK 2023-01-18 2023 /pmc/articles/PMC9935384/ /pubmed/36653475 http://dx.doi.org/10.1038/s41435-023-00194-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Brief Communication Merk, Verena M. Grob, Leonie Fleischmann, Achim Brunner, Thomas Human lung carcinomas synthesize immunoregulatory glucocorticoids |
title | Human lung carcinomas synthesize immunoregulatory glucocorticoids |
title_full | Human lung carcinomas synthesize immunoregulatory glucocorticoids |
title_fullStr | Human lung carcinomas synthesize immunoregulatory glucocorticoids |
title_full_unstemmed | Human lung carcinomas synthesize immunoregulatory glucocorticoids |
title_short | Human lung carcinomas synthesize immunoregulatory glucocorticoids |
title_sort | human lung carcinomas synthesize immunoregulatory glucocorticoids |
topic | Brief Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9935384/ https://www.ncbi.nlm.nih.gov/pubmed/36653475 http://dx.doi.org/10.1038/s41435-023-00194-y |
work_keys_str_mv | AT merkverenam humanlungcarcinomassynthesizeimmunoregulatoryglucocorticoids AT grobleonie humanlungcarcinomassynthesizeimmunoregulatoryglucocorticoids AT fleischmannachim humanlungcarcinomassynthesizeimmunoregulatoryglucocorticoids AT brunnerthomas humanlungcarcinomassynthesizeimmunoregulatoryglucocorticoids |