Metabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment

Sasidharan Nair, V, Saleh, R, Toor, SM, Cyprian, FS and Elkord, E ORCID: https://orcid.org/0000-0002-3868-0318 2021, 'Metabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment' , Cancer immunology, immunotherapy, 70 (8) , pp. 2103-2121.

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Abstract

Metabolic dysregulation in the hypoxic tumor microenvironment (TME) is considered as a hallmark of solid tumors, leading to changes in biosynthetic pathways favoring onset, survival and proliferation of malignant cells. Within the TME, hypoxic milieu favors metabolic reprogramming of tumor cells, which subsequently affects biological properties of tumor-infiltrating immune cells. T regulatory cells (Tregs), including both circulating and tissue-resident cells, are particularly susceptible to hypoxic metabolic signaling that can reprogram their biological and physicochemical properties. Furthermore, metabolic reprogramming modifies Tregs to utilize alternative substrates and undergo a plethora of metabolic events to meet their energy demands. Major impact of this metabolic reprogramming can result in differentiation, survival, excessive secretion of immunosuppressive cytokines and proliferation of Tregs within the TME, which in turn dampen anti-tumor immune responses. Studies on fine-tuning of Treg metabolism are challenging due to heterogenicity of tissue-resident Tregs and their dynamic functions. In this review, we highlight tumor intrinsic and extrinsic factors, which can influence Treg metabolism in the hypoxic TME. Moreover, we focus on metabolic reprogramming of Tregs that could unveil potential regulatory networks favoring tumorigenesis/progression, and provide novel insights, including inhibitors against acetyl-coA carboxylase 1 and transforming growth factor beta into targeting Treg metabolism for therapeutic benefits.

Item Type: Article
Additional Information: ** From PubMed via Jisc Publications Router **Journal IDs: eissn 1432-0851 **Article IDs: pubmed: 33532902; pii: 10.1007/s00262-020-02842-y **History: accepted 21-12-2020; submitted 30-09-2020
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Cancer immunology, immunotherapy
Publisher: Springer
ISSN: 0340-7004
Related URLs:
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 04 May 2021 14:14
Last Modified: 28 Aug 2021 11:05
URI: http://usir.salford.ac.uk/id/eprint/59602

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