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Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity
Polyamines are ubiquitous, amine-rich molecules with diverse processes in biology. Recent work has highlighted that polyamines exert profound roles on the mammalian immune system, particularly inflammation and cancer. The mechanisms by which they control immunity are still being described. In the co...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909056/ https://www.ncbi.nlm.nih.gov/pubmed/35269518 http://dx.doi.org/10.3390/cells11050896 |
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author | Chia, Tzu-yi Zolp, Andrew Miska, Jason |
author_facet | Chia, Tzu-yi Zolp, Andrew Miska, Jason |
author_sort | Chia, Tzu-yi |
collection | PubMed |
description | Polyamines are ubiquitous, amine-rich molecules with diverse processes in biology. Recent work has highlighted that polyamines exert profound roles on the mammalian immune system, particularly inflammation and cancer. The mechanisms by which they control immunity are still being described. In the context of inflammation and autoimmunity, polyamine levels inversely correlate to autoimmune phenotypes, with lower polyamine levels associated with higher inflammatory responses. Conversely, in the context of cancer, polyamines and polyamine biosynthetic genes positively correlate with the severity of malignancy. Blockade of polyamine metabolism in cancer results in reduced tumor growth, and the effects appear to be mediated by an increase in T-cell infiltration and a pro-inflammatory phenotype of macrophages. These studies suggest that polyamine depletion leads to inflammation and that polyamine enrichment potentiates myeloid cell immune suppression. Indeed, combinatorial treatment with polyamine blockade and immunotherapy has shown efficacy in pre-clinical models of cancer. Considering the efficacy of immunotherapies is linked to autoimmune sequelae in humans, termed immune-adverse related events (iAREs), this suggests that polyamine levels may govern the inflammatory response to immunotherapies. This review proposes that polyamine metabolism acts to balance autoimmune inflammation and anti-tumor immunity and that polyamine levels can be used to monitor immune responses and responsiveness to immunotherapy. |
format | Online Article Text |
id | pubmed-8909056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89090562022-03-11 Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity Chia, Tzu-yi Zolp, Andrew Miska, Jason Cells Review Polyamines are ubiquitous, amine-rich molecules with diverse processes in biology. Recent work has highlighted that polyamines exert profound roles on the mammalian immune system, particularly inflammation and cancer. The mechanisms by which they control immunity are still being described. In the context of inflammation and autoimmunity, polyamine levels inversely correlate to autoimmune phenotypes, with lower polyamine levels associated with higher inflammatory responses. Conversely, in the context of cancer, polyamines and polyamine biosynthetic genes positively correlate with the severity of malignancy. Blockade of polyamine metabolism in cancer results in reduced tumor growth, and the effects appear to be mediated by an increase in T-cell infiltration and a pro-inflammatory phenotype of macrophages. These studies suggest that polyamine depletion leads to inflammation and that polyamine enrichment potentiates myeloid cell immune suppression. Indeed, combinatorial treatment with polyamine blockade and immunotherapy has shown efficacy in pre-clinical models of cancer. Considering the efficacy of immunotherapies is linked to autoimmune sequelae in humans, termed immune-adverse related events (iAREs), this suggests that polyamine levels may govern the inflammatory response to immunotherapies. This review proposes that polyamine metabolism acts to balance autoimmune inflammation and anti-tumor immunity and that polyamine levels can be used to monitor immune responses and responsiveness to immunotherapy. MDPI 2022-03-05 /pmc/articles/PMC8909056/ /pubmed/35269518 http://dx.doi.org/10.3390/cells11050896 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Chia, Tzu-yi Zolp, Andrew Miska, Jason Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity |
title | Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity |
title_full | Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity |
title_fullStr | Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity |
title_full_unstemmed | Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity |
title_short | Polyamine Immunometabolism: Central Regulators of Inflammation, Cancer and Autoimmunity |
title_sort | polyamine immunometabolism: central regulators of inflammation, cancer and autoimmunity |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909056/ https://www.ncbi.nlm.nih.gov/pubmed/35269518 http://dx.doi.org/10.3390/cells11050896 |
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