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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Vydané v:	EBioMedicine Ročník 73; s. 103627
Hlavní autori:	Wang, Zi-Hao, Peng, Wen-Bei, Zhang, Pei, Yang, Xiang-Ping, Zhou, Qiong
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Netherlands Elsevier B.V 01.11.2021 Elsevier
Predmet:	Advanced Basic Science Animals Biological Transport Biomarkers Cancer immunity Cancer metabolism Disease Management Disease Susceptibility Energy Metabolism Glycolysis Glycolytic enzymes Humans Immunomodulation Immunotherapy Internal Medicine Lactate Lactic Acid - metabolism Metabolic Networks and Pathways Monocarboxylate transporters Neoplasms - etiology Neoplasms - metabolism Neoplasms - pathology Neoplasms - therapy Review Tumor Microenvironment - immunology Tumour microenvironment Lactate Monocarboxylate transporters Cancer metabolism Cancer immunity Glycolytic enzymes Tumour microenvironment
ISSN:	2352-3964, 2352-3964
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 These authors contributed equally to this review.
ISSN:	2352-3964 2352-3964
DOI:	10.1016/j.ebiom.2021.103627