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Metabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment

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submitted on 2024-04-28, 06:40 and posted on 2024-05-05, 10:36 authored by Varun Sasidharan Nair, Reem Saleh, Salman M. Toor, Farhan S. Cyprian, Eyad Elkord

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.

Correction: Metabolic reprogramming of T regulatory cells in the hypoxic tumor microenvironment. https://dx.doi.org/10.1007/s00262-021-02999-0, published online 07 July 2021.

Other Information

Published in: Cancer Immunology, Immunotherapy
License: https://creativecommons.org/licenses/by/4.0
See article on publisher's website: https://dx.doi.org/10.1007/s00262-020-02842-y

History

Language

  • English

Publisher

Springer Nature

Publication Year

  • 2021

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute - HBKU
  • Cancer Research Center - QBRI
  • Qatar University
  • Qatar University Health - QU
  • College of Medicine - QU HEALTH

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