Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors
During metabolic reprogramming, glioma cells and their initiating cells efficiently utilized carbohydrates, lipids and amino acids in the hypoxic lesions, which not only ensured sufficient energy for rapid growth and improved the migration to normal brain tissues, but also altered the role of immune...
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2021-06-01
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doaj-d22d6f7c7ed9416b92441cc7836b759d2021-06-15T08:48:04ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-06-01910.3389/fcell.2021.693215693215Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral TumorsRunze Qiu0Yue Zhong1Qingquan Li2Yingbin Li3Hongwei Fan4Department of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing, ChinaCenter of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Clinical Pharmacology Lab, Nanjing First Hospital, Nanjing Medical University, Nanjing, ChinaDuring metabolic reprogramming, glioma cells and their initiating cells efficiently utilized carbohydrates, lipids and amino acids in the hypoxic lesions, which not only ensured sufficient energy for rapid growth and improved the migration to normal brain tissues, but also altered the role of immune cells in tumor microenvironment. Glioma cells secreted interferential metabolites or depriving nutrients to injure the tumor recognition, phagocytosis and lysis of glioma-associated microglia/macrophages (GAMs), cytotoxic T lymphocytes, natural killer cells and dendritic cells, promoted the expansion and infiltration of immunosuppressive regulatory T cells and myeloid-derived suppressor cells, and conferred immune silencing phenotypes on GAMs and dendritic cells. The overexpressed metabolic enzymes also increased the secretion of chemokines to attract neutrophils, regulatory T cells, GAMs, and dendritic cells, while weakening the recruitment of cytotoxic T lymphocytes and natural killer cells, which activated anti-inflammatory and tolerant mechanisms and hindered anti-tumor responses. Therefore, brain-targeted metabolic therapy may improve glioma immunity. This review will clarify the metabolic properties of glioma cells and their interactions with tumor microenvironment immunity, and discuss the application strategies of metabolic therapy in glioma immune silence and escape.https://www.frontiersin.org/articles/10.3389/fcell.2021.693215/fullgliomametabolic reprogrammingtumor microenvironmentimmune escapemetabolic therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Runze Qiu Yue Zhong Qingquan Li Yingbin Li Hongwei Fan |
spellingShingle |
Runze Qiu Yue Zhong Qingquan Li Yingbin Li Hongwei Fan Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors Frontiers in Cell and Developmental Biology glioma metabolic reprogramming tumor microenvironment immune escape metabolic therapy |
author_facet |
Runze Qiu Yue Zhong Qingquan Li Yingbin Li Hongwei Fan |
author_sort |
Runze Qiu |
title |
Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors |
title_short |
Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors |
title_full |
Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors |
title_fullStr |
Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors |
title_full_unstemmed |
Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors |
title_sort |
metabolic remodeling in glioma immune microenvironment: intercellular interactions distinct from peripheral tumors |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-06-01 |
description |
During metabolic reprogramming, glioma cells and their initiating cells efficiently utilized carbohydrates, lipids and amino acids in the hypoxic lesions, which not only ensured sufficient energy for rapid growth and improved the migration to normal brain tissues, but also altered the role of immune cells in tumor microenvironment. Glioma cells secreted interferential metabolites or depriving nutrients to injure the tumor recognition, phagocytosis and lysis of glioma-associated microglia/macrophages (GAMs), cytotoxic T lymphocytes, natural killer cells and dendritic cells, promoted the expansion and infiltration of immunosuppressive regulatory T cells and myeloid-derived suppressor cells, and conferred immune silencing phenotypes on GAMs and dendritic cells. The overexpressed metabolic enzymes also increased the secretion of chemokines to attract neutrophils, regulatory T cells, GAMs, and dendritic cells, while weakening the recruitment of cytotoxic T lymphocytes and natural killer cells, which activated anti-inflammatory and tolerant mechanisms and hindered anti-tumor responses. Therefore, brain-targeted metabolic therapy may improve glioma immunity. This review will clarify the metabolic properties of glioma cells and their interactions with tumor microenvironment immunity, and discuss the application strategies of metabolic therapy in glioma immune silence and escape. |
topic |
glioma metabolic reprogramming tumor microenvironment immune escape metabolic therapy |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.693215/full |
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