Lactate in the tumour microenvironment: From immune modulation to therapy

Disordered metabolic states, which are characterised by hypoxia and elevated levels of metabolites, particularly lactate, contribute to the immunosuppression in the tumour microenvironment (TME). Excessive lactate secreted by metabolism-reprogrammed cancer cells regulates immune responses via causin...

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Autores principales: Wang, Zi-Hao, Peng, Wen-Bei, Zhang, Pei, Yang, Xiang-Ping, Zhou, Qiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524104/
https://www.ncbi.nlm.nih.gov/pubmed/34656878
http://dx.doi.org/10.1016/j.ebiom.2021.103627
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author Wang, Zi-Hao
Peng, Wen-Bei
Zhang, Pei
Yang, Xiang-Ping
Zhou, Qiong
author_facet Wang, Zi-Hao
Peng, Wen-Bei
Zhang, Pei
Yang, Xiang-Ping
Zhou, Qiong
author_sort Wang, Zi-Hao
collection PubMed
description Disordered metabolic states, which are characterised by hypoxia and elevated levels of metabolites, particularly lactate, contribute to the immunosuppression in the tumour microenvironment (TME). Excessive lactate secreted by metabolism-reprogrammed cancer cells regulates immune responses via causing extracellular acidification, acting as an energy source by shuttling between different cell populations, and inhibiting the mechanistic (previously ‘mammalian’) target of rapamycin (mTOR) pathway in immune cells. This review focuses on recent advances in the regulation of immune responses by lactate, as well as therapeutic strategies targeting lactate anabolism and transport in the TME, such as those involving glycolytic enzymes and monocarboxylate transporter inhibitors. Considering the multifaceted roles of lactate in cancer metabolism, a comprehensive understanding of how lactate and lactate-targeting therapies regulate immune responses in the TME will provide insights into the complex relationships between metabolism and antitumour immunity.
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spelling pubmed-85241042021-10-25 Lactate in the tumour microenvironment: From immune modulation to therapy Wang, Zi-Hao Peng, Wen-Bei Zhang, Pei Yang, Xiang-Ping Zhou, Qiong EBioMedicine Review Disordered metabolic states, which are characterised by hypoxia and elevated levels of metabolites, particularly lactate, contribute to the immunosuppression in the tumour microenvironment (TME). Excessive lactate secreted by metabolism-reprogrammed cancer cells regulates immune responses via causing extracellular acidification, acting as an energy source by shuttling between different cell populations, and inhibiting the mechanistic (previously ‘mammalian’) target of rapamycin (mTOR) pathway in immune cells. This review focuses on recent advances in the regulation of immune responses by lactate, as well as therapeutic strategies targeting lactate anabolism and transport in the TME, such as those involving glycolytic enzymes and monocarboxylate transporter inhibitors. Considering the multifaceted roles of lactate in cancer metabolism, a comprehensive understanding of how lactate and lactate-targeting therapies regulate immune responses in the TME will provide insights into the complex relationships between metabolism and antitumour immunity. Elsevier 2021-10-14 /pmc/articles/PMC8524104/ /pubmed/34656878 http://dx.doi.org/10.1016/j.ebiom.2021.103627 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review
Wang, Zi-Hao
Peng, Wen-Bei
Zhang, Pei
Yang, Xiang-Ping
Zhou, Qiong
Lactate in the tumour microenvironment: From immune modulation to therapy
title Lactate in the tumour microenvironment: From immune modulation to therapy
title_full Lactate in the tumour microenvironment: From immune modulation to therapy
title_fullStr Lactate in the tumour microenvironment: From immune modulation to therapy
title_full_unstemmed Lactate in the tumour microenvironment: From immune modulation to therapy
title_short Lactate in the tumour microenvironment: From immune modulation to therapy
title_sort lactate in the tumour microenvironment: from immune modulation to therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524104/
https://www.ncbi.nlm.nih.gov/pubmed/34656878
http://dx.doi.org/10.1016/j.ebiom.2021.103627
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