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胶质母细胞瘤微环境中髓样细胞的代谢适应

Metabolic adaptation of myeloid cells in the glioblastoma microenvironment.

作者信息

Essakhi Nora, Bertucci Alexandre, Baeza-Kallee Nathalie, Colin Carole, Lavignolle-Heguy Rosario, Garcia-Gonzalez Paulina, Argüello Rafael J, Tchoghandjian Aurélie, Tabouret Emeline

机构信息

Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, GlioME Team, Marseille, France.

APHM, CHU Timone, Service de Neurooncologie, Marseille, France.

出版信息

Front Immunol. 2024 Dec 23;15:1431112. doi: 10.3389/fimmu.2024.1431112. eCollection 2024.


DOI:10.3389/fimmu.2024.1431112
PMID:39763643
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11700814/
Abstract

In recent decades, immunometabolism in cancers has emerged as an interesting target for treatment development. Indeed, the tumor microenvironment (TME) unique characteristics such as hypoxia and limitation of nutrients availability lead to a switch in metabolic pathways in both tumor and TME cells in order to support their adaptation and grow. Glioblastoma (GBM), the most frequent and aggressive primary brain tumor in adults, has been extensively studied in multiple aspects regarding its immune population, but research focused on immunometabolism remains limited. Here, we provide an overview of immunometabolism adaptation of myeloid cells in cancers with a specific focus on GBM and other brain tumors, before describing current therapeutic strategies targeting metabolic pathways. The main myeloid cells composing the GBM TME include tumor-associated macrophages (TAMs), which comprise both peripheral macrophages and local microglia, as well as myeloid-derived suppressor cells. The metabolic pathways involved in myeloid cell remodeling encompass the tricarboxylic acid cycle (TCA cycle), the lipid, glucose and amino acid metabolism and hypoxia. Developing treatments that target these metabolic pathways in tumor growth and its TME is a promising and increasing field. It includes both drug-repurposing and the development of innovative metabolic therapies. We finally provide an overview of all clinical trials in neuro-oncology involving treatments modifying cell metabolism and provide the preclinical rationale for both drugs already evaluated within clinical trials and potential candidates for future trials.

摘要

近几十年来,癌症中的免疫代谢已成为治疗开发的一个有趣靶点。事实上,肿瘤微环境(TME)的独特特征,如缺氧和营养物质供应受限,导致肿瘤细胞和TME细胞中的代谢途径发生转变,以支持它们的适应和生长。胶质母细胞瘤(GBM)是成人中最常见、侵袭性最强的原发性脑肿瘤,在其免疫群体的多个方面都得到了广泛研究,但专注于免疫代谢的研究仍然有限。在这里,我们概述了癌症中髓系细胞的免疫代谢适应情况,特别关注GBM和其他脑肿瘤,然后描述了目前针对代谢途径的治疗策略。构成GBM TME的主要髓系细胞包括肿瘤相关巨噬细胞(TAM),它包括外周巨噬细胞和局部小胶质细胞,以及髓系来源的抑制细胞。参与髓系细胞重塑的代谢途径包括三羧酸循环(TCA循环)、脂质、葡萄糖和氨基酸代谢以及缺氧。开发针对肿瘤生长及其TME中这些代谢途径的治疗方法是一个有前景且不断发展的领域。这包括药物重新利用和创新代谢疗法的开发。我们最后概述了神经肿瘤学中所有涉及改变细胞代谢治疗的临床试验,并为已在临床试验中评估的药物以及未来试验的潜在候选药物提供临床前依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/352d/11700814/7e3b78472c4d/fimmu-15-1431112-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/352d/11700814/fb7c159e8a61/fimmu-15-1431112-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/352d/11700814/7e3b78472c4d/fimmu-15-1431112-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/352d/11700814/fb7c159e8a61/fimmu-15-1431112-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/352d/11700814/7e3b78472c4d/fimmu-15-1431112-g002.jpg

相似文献

[1]
Metabolic adaptation of myeloid cells in the glioblastoma microenvironment.

Front Immunol. 2024-12-23

[2]
Macrophages and microglia: the cerberus of glioblastoma.

Acta Neuropathol Commun. 2021-3-25

[3]
Changes in the tumor microenvironment and outcome for TME-targeting therapy in glioblastoma: A pilot study.

PLoS One. 2021

[4]
Altered Metabolism in Glioblastoma: Myeloid-Derived Suppressor Cell (MDSC) Fitness and Tumor-Infiltrating Lymphocyte (TIL) Dysfunction.

Int J Mol Sci. 2021-4-24

[5]
Myeloid Cells in Glioblastoma Microenvironment.

Cells. 2020-12-24

[6]
Neuroinflammation in Glioblastoma: The Role of the Microenvironment in Tumour Progression.

Curr Cancer Drug Targets. 2024

[7]
GBM Immunotherapy: Macrophage Impacts.

Immunol Invest. 2024-7

[8]
Targeting HIF-2α in glioblastoma reshapes the immune infiltrate and enhances response to immune checkpoint blockade.

Cell Mol Life Sci. 2025-3-17

[9]
The FKBP51s Splice Isoform Predicts Unfavorable Prognosis in Patients with Glioblastoma.

Cancer Res Commun. 2024-5-16

[10]
Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts.

Genome Med. 2024-4-2

引用本文的文献

[1]
Liposomal honokiol enhance the anti-tumor effect of bevacizumab in glioblastoma by inhibiting autophagy.

Future Sci OA. 2025-12

本文引用的文献

[1]
A novel insight into cancer therapy: Lipid metabolism in tumor-associated macrophages.

Int Immunopharmacol. 2024-6-30

[2]
Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma.

Immunity. 2024-5-14

[3]
Cancer cell metabolism and antitumour immunity.

Nat Rev Immunol. 2024-9

[4]
Evaluating Leukocyte Telomere Length and Myeloid-Derived Suppressor Cells as Biomarkers for Prostate Cancer.

Cancers (Basel). 2024-3-31

[5]
Targeting lipid metabolism of macrophages: A new strategy for tumor therapy.

J Adv Res. 2025-2

[6]
High monocytic MDSC signature predicts multi-drug resistance and cancer relapse in non-Hodgkin lymphoma patients treated with R-CHOP.

Front Immunol. 2023

[7]
ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells.

Acta Pharm Sin B. 2023-12

[8]
The immune cell landscape of glioblastoma patients highlights a myeloid-enriched and immune suppressed microenvironment compared to metastatic brain tumors.

Front Immunol. 2023

[9]
The local microenvironment drives activation of neutrophils in human brain tumors.

Cell. 2023-10-12

[10]
Measuring the Metabolic State of Tissue-Resident Macrophages via SCENITH.

Methods Mol Biol. 2024

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