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Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment
Contrary to the “obesity paradox,” which arises from retrospective studies relying on body mass index to define obesity, epidemiologic evidence suggests central or visceral obesity is associated with a higher risk for the development of lung cancer. About 60% of individuals at high risk for developi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598035/ https://www.ncbi.nlm.nih.gov/pubmed/36289552 http://dx.doi.org/10.1186/s40170-022-00292-x |
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author | Rosario, Spencer R. Smith, Randall J. Patnaik, Santosh K. Liu, Song Barbi, Joseph Yendamuri, Sai |
author_facet | Rosario, Spencer R. Smith, Randall J. Patnaik, Santosh K. Liu, Song Barbi, Joseph Yendamuri, Sai |
author_sort | Rosario, Spencer R. |
collection | PubMed |
description | Contrary to the “obesity paradox,” which arises from retrospective studies relying on body mass index to define obesity, epidemiologic evidence suggests central or visceral obesity is associated with a higher risk for the development of lung cancer. About 60% of individuals at high risk for developing lung cancer or those already with early-stage disease are either overweight or obese. Findings from resected patient tumors and mouse lung tumor models show obesity dampens immune activity in the tumor microenvironment (TME) encouraging disease progression. In line with this, we have observed a marked, obesity-specific enhancement in the presence and phenotype of immunosuppressive regulatory T (Treg) cells in murine tumors as well as the airways of both humans and mice. Leveraging direct metabolomic measurements and robust inferred analyses from RNA-sequencing data, we here demonstrate for the first time that visceral adiposity alters the lung microenvironment via dysregulated acetyl-CoA metabolism in a direction that facilitates immune suppression and lung carcinogenesis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40170-022-00292-x. |
format | Online Article Text |
id | pubmed-9598035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-95980352022-10-27 Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment Rosario, Spencer R. Smith, Randall J. Patnaik, Santosh K. Liu, Song Barbi, Joseph Yendamuri, Sai Cancer Metab Brief Report Contrary to the “obesity paradox,” which arises from retrospective studies relying on body mass index to define obesity, epidemiologic evidence suggests central or visceral obesity is associated with a higher risk for the development of lung cancer. About 60% of individuals at high risk for developing lung cancer or those already with early-stage disease are either overweight or obese. Findings from resected patient tumors and mouse lung tumor models show obesity dampens immune activity in the tumor microenvironment (TME) encouraging disease progression. In line with this, we have observed a marked, obesity-specific enhancement in the presence and phenotype of immunosuppressive regulatory T (Treg) cells in murine tumors as well as the airways of both humans and mice. Leveraging direct metabolomic measurements and robust inferred analyses from RNA-sequencing data, we here demonstrate for the first time that visceral adiposity alters the lung microenvironment via dysregulated acetyl-CoA metabolism in a direction that facilitates immune suppression and lung carcinogenesis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40170-022-00292-x. BioMed Central 2022-10-26 /pmc/articles/PMC9598035/ /pubmed/36289552 http://dx.doi.org/10.1186/s40170-022-00292-x Text en © The Author(s) 2022 https://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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Brief Report Rosario, Spencer R. Smith, Randall J. Patnaik, Santosh K. Liu, Song Barbi, Joseph Yendamuri, Sai Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment |
title | Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment |
title_full | Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment |
title_fullStr | Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment |
title_full_unstemmed | Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment |
title_short | Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment |
title_sort | altered acetyl-coa metabolism presents a new potential immunotherapy target in the obese lung microenvironment |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9598035/ https://www.ncbi.nlm.nih.gov/pubmed/36289552 http://dx.doi.org/10.1186/s40170-022-00292-x |
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