Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints

Immune checkpoint inhibitors (ICIs), Ipilimumab, Nivolumab, Pembrolizumab and Atezolizumab, have been applied in anti-tumor therapy and demonstrated exciting performance compared to conventional treatments. However, the unsatisfactory response rates, high recurrence and adaptive resistance limit the...

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Autores principales:	Yaolin Xu, Lijie He, Qiang Fu, Junzhe Hu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	glycolysis amino acid metabolism lipid metabolism nucleotide metabolism mitochondrial biogenesis the tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/4593b770644d4d20a393ea8ad3438eb1
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spelling	oai:doaj.org-article:4593b770644d4d20a393ea8ad3438eb12021-11-11T08:14:33ZMetabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints2234-943X10.3389/fonc.2021.759015https://doaj.org/article/4593b770644d4d20a393ea8ad3438eb12021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.759015/fullhttps://doaj.org/toc/2234-943XImmune checkpoint inhibitors (ICIs), Ipilimumab, Nivolumab, Pembrolizumab and Atezolizumab, have been applied in anti-tumor therapy and demonstrated exciting performance compared to conventional treatments. However, the unsatisfactory response rates, high recurrence and adaptive resistance limit their benefits. Metabolic reprogramming appears to be one of the crucial barriers to immunotherapy. The deprivation of required nutrients and altered metabolites not only promote tumor progression but also confer dysfunction on immune cells in the tumor microenvironment (TME). Glycolysis plays a central role in metabolic reprogramming and immunoregulation in the TME, and many therapies targeting glycolysis have been developed, and their combinations with ICIs are in preclinical and clinical trials. Additional attention has been paid to the role of amino acids, lipids, nucleotides and mitochondrial biogenesis in metabolic reprogramming and clinical anti-tumor therapy. This review attempts to describe reprogramming metabolisms within tumor cells and immune cells, from the aspects of glycolysis, amino acid metabolism, lipid metabolism, nucleotide metabolism and mitochondrial biogenesis and their impact on immunity in the TME, as well as the significance of targeting metabolism in anti-tumor therapy, especially in combination with ICIs. In particular, we highlight the expression mechanism of programmed cell death (ligand) 1 [PD-(L)1] in tumor cells and immune cells under reprogramming metabolism, and discuss in detail the potential of targeting key metabolic pathways to break resistance and improve the efficacy of ICIs based on results from current preclinical and clinical trials. Besides, we draw out biomarkers of potential predictive value in ICIs treatment from a metabolic perspective.Yaolin XuLijie HeQiang FuJunzhe HuFrontiers Media S.A.articleglycolysisamino acid metabolismlipid metabolismnucleotide metabolismmitochondrial biogenesisthe tumor microenvironmentNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glycolysis amino acid metabolism lipid metabolism nucleotide metabolism mitochondrial biogenesis the tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	glycolysis amino acid metabolism lipid metabolism nucleotide metabolism mitochondrial biogenesis the tumor microenvironment Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yaolin Xu Lijie He Qiang Fu Junzhe Hu Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints
description	Immune checkpoint inhibitors (ICIs), Ipilimumab, Nivolumab, Pembrolizumab and Atezolizumab, have been applied in anti-tumor therapy and demonstrated exciting performance compared to conventional treatments. However, the unsatisfactory response rates, high recurrence and adaptive resistance limit their benefits. Metabolic reprogramming appears to be one of the crucial barriers to immunotherapy. The deprivation of required nutrients and altered metabolites not only promote tumor progression but also confer dysfunction on immune cells in the tumor microenvironment (TME). Glycolysis plays a central role in metabolic reprogramming and immunoregulation in the TME, and many therapies targeting glycolysis have been developed, and their combinations with ICIs are in preclinical and clinical trials. Additional attention has been paid to the role of amino acids, lipids, nucleotides and mitochondrial biogenesis in metabolic reprogramming and clinical anti-tumor therapy. This review attempts to describe reprogramming metabolisms within tumor cells and immune cells, from the aspects of glycolysis, amino acid metabolism, lipid metabolism, nucleotide metabolism and mitochondrial biogenesis and their impact on immunity in the TME, as well as the significance of targeting metabolism in anti-tumor therapy, especially in combination with ICIs. In particular, we highlight the expression mechanism of programmed cell death (ligand) 1 [PD-(L)1] in tumor cells and immune cells under reprogramming metabolism, and discuss in detail the potential of targeting key metabolic pathways to break resistance and improve the efficacy of ICIs based on results from current preclinical and clinical trials. Besides, we draw out biomarkers of potential predictive value in ICIs treatment from a metabolic perspective.
format	article
author	Yaolin Xu Lijie He Qiang Fu Junzhe Hu
author_facet	Yaolin Xu Lijie He Qiang Fu Junzhe Hu
author_sort	Yaolin Xu
title	Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints
title_short	Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints
title_full	Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints
title_fullStr	Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints
title_full_unstemmed	Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints
title_sort	metabolic reprogramming in the tumor microenvironment with immunocytes and immune checkpoints
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/4593b770644d4d20a393ea8ad3438eb1
work_keys_str_mv	AT yaolinxu metabolicreprogramminginthetumormicroenvironmentwithimmunocytesandimmunecheckpoints AT lijiehe metabolicreprogramminginthetumormicroenvironmentwithimmunocytesandimmunecheckpoints AT qiangfu metabolicreprogramminginthetumormicroenvironmentwithimmunocytesandimmunecheckpoints AT junzhehu metabolicreprogramminginthetumormicroenvironmentwithimmunocytesandimmunecheckpoints
_version_	1718439305018343424

Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints

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