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脑胶质瘤相关巨噬细胞的起源、激活和靶向治疗。

Origin, activation, and targeted therapy of glioma-associated macrophages.

机构信息

School of Clinical Medicine, Hebei University, Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China.

Hebei Key Laboratory of Precise Diagnosis and Treatment of Glioma, Baoding, China.

出版信息

Front Immunol. 2022 Oct 6;13:974996. doi: 10.3389/fimmu.2022.974996. eCollection 2022.


DOI:10.3389/fimmu.2022.974996
PMID:36275720
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9582955/
Abstract

The glioma tumor microenvironment plays a crucial role in the development, occurrence, and treatment of gliomas. Glioma-associated macrophages (GAMs) are the most widely infiltrated immune cells in the tumor microenvironment (TME) and one of the major cell populations that exert immune functions. GAMs typically originate from two cell types-brain-resident microglia (BRM) and bone marrow-derived monocytes (BMDM), depending on a variety of cytokines for recruitment and activation. GAMs mainly contain two functionally and morphologically distinct activation types- classically activated M1 macrophages (antitumor/immunostimulatory) and alternatively activated M2 macrophages (protumor/immunosuppressive). GAMs have been shown to affect multiple biological functions of gliomas, including promoting tumor growth and invasion, angiogenesis, energy metabolism, and treatment resistance. Both M1 and M2 macrophages are highly plastic and can polarize or interconvert under various malignant conditions. As the relationship between GAMs and gliomas has become more apparent, GAMs have long been one of the promising targets for glioma therapy, and many studies have demonstrated the therapeutic potential of this target. Here, we review the origin and activation of GAMs in gliomas, how they regulate tumor development and response to therapies, and current glioma therapeutic strategies targeting GAMs.

摘要

脑胶质瘤肿瘤微环境在脑胶质瘤的发生、发展和治疗中起着至关重要的作用。脑胶质瘤相关巨噬细胞(GAMs)是肿瘤微环境(TME)中最广泛浸润的免疫细胞之一,也是发挥免疫功能的主要细胞群体之一。GAMs 通常起源于两种细胞类型——脑固有小胶质细胞(BRM)和骨髓来源的单核细胞(BMDM),根据各种细胞因子的募集和激活,GAMs 主要包含两种功能和形态上明显不同的激活类型——经典激活的 M1 巨噬细胞(抗肿瘤/免疫刺激)和交替激活的 M2 巨噬细胞(促肿瘤/免疫抑制)。GAMs 已被证明会影响脑胶质瘤的多种生物学功能,包括促进肿瘤生长和侵袭、血管生成、能量代谢和治疗耐药性。M1 和 M2 巨噬细胞都具有高度的可塑性,在各种恶性条件下可以极化或相互转化。随着 GAMs 与脑胶质瘤之间的关系变得更加明显,GAMs 一直是脑胶质瘤治疗的有前途的靶点之一,许多研究已经证明了该靶点的治疗潜力。在这里,我们综述了 GAMs 在脑胶质瘤中的起源和激活、它们如何调节肿瘤的发生和对治疗的反应,以及目前针对 GAMs 的脑胶质瘤治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eea/9582955/8ffffacb3726/fimmu-13-974996-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eea/9582955/9167e2ba27db/fimmu-13-974996-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eea/9582955/8ffffacb3726/fimmu-13-974996-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eea/9582955/9167e2ba27db/fimmu-13-974996-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eea/9582955/8ffffacb3726/fimmu-13-974996-g002.jpg

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本文引用的文献

[1]
Dual-sgRNA CRISPR/Cas9 knockout of PD-L1 in human U87 glioblastoma tumor cells inhibits proliferation, invasion, and tumor-associated macrophage polarization.

Sci Rep. 2022-2-14

[2]
Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target.

Nat Commun. 2022-2-9

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Current and Emerging Strategies for Enhancing Antibody Delivery to the Brain.

Pharmaceutics. 2021-11-26

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Int J Mol Sci. 2021-10-16

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Glioblastoma Cell-Derived lncRNA-Containing Exosomes Induce Microglia to Produce Complement C5, Promoting Chemotherapy Resistance.

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Tumor Associated Macrophages, as the Dominant Immune Cells, Are an Indispensable Target for Immunologically Cold Tumor-Glioma Therapy?

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Neurooncol Adv. 2021-5-4

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Brain Tumor Pathol. 2021-7

[10]
SLIT2/ROBO signaling in tumor-associated microglia and macrophages drives glioblastoma immunosuppression and vascular dysmorphia.

J Clin Invest. 2021-8-16

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