Macrophages in Glioblastoma Development and Therapy: A Double-Edged Sword

Wu, Mengwan; Shi, Ying; Zhu, Longjiao; Chen, Luoyi; Zhao, Xinchen; Xu, Chuan

doi:10.3390/life12081225

Cited by 11 publications

(7 citation statements)

References 137 publications

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“…As already described by other teams, we observed in U87 glioma xenografts in vivo, a protumoral environment characterized by a majority of M2 phenotype that could promote angiogenesis and tumor malignancy [ 47 , 48 ]. Interestingly, when using AGuIX@PS@KDKPPR nanoparticles in vivo, we previously visualized tumor tissue by T1-weighted imaging and illuminated it by interstitial stereotactic PDT [ 5 ].…”

Section: Discussionmentioning

confidence: 59%

Targeting Glioblastoma-Associated Macrophages for Photodynamic Therapy Using AGuIX®-Design Nanoparticles

et al. 2023

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Glioblastoma (GBM) is the most difficult brain cancer to treat, and photodynamic therapy (PDT) is emerging as a complementary approach to improve tumor eradication. Neuropilin-1 (NRP-1) protein expression plays a critical role in GBM progression and immune response. Moreover, various clinical databases highlight a relationship between NRP-1 and M2 macrophage infiltration. In order to induce a photodynamic effect, multifunctional AGuIX®-design nanoparticles were used in combination with a magnetic resonance imaging (MRI) contrast agent, as well as a porphyrin as the photosensitizer molecule and KDKPPR peptide ligand for targeting the NRP-1 receptor. The main objective of this study was to characterize the impact of macrophage NRP-1 protein expression on the uptake of functionalized AGuIX®-design nanoparticles in vitro and to describe the influence of GBM cell secretome post-PDT on the polarization of macrophages into M1 or M2 phenotypes. By using THP-1 human monocytes, successful polarization into the macrophage phenotypes was argued via specific morphological traits, discriminant nucleocytoplasmic ratio values, and different adhesion abilities based on real-time cell impedance measurements. In addition, macrophage polarization was confirmed via the transcript-level expression of TNFα, CXCL10, CD-80, CD-163, CD-206, and CCL22 markers. In relation to NRP-1 protein over-expression, we demonstrated a three-fold increase in functionalized nanoparticle uptake for the M2 macrophages compared to the M1 phenotype. The secretome of the post-PDT GBM cells led to nearly a three-fold increase in the over-expression of TNFα transcripts, confirming the polarization to the M1 phenotype. The in vivo relationship between post-PDT efficiency and the inflammatory effects points to the extensive involvement of macrophages in the tumor zone.

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Section: Discussionmentioning

confidence: 59%

Targeting Glioblastoma-Associated Macrophages for Photodynamic Therapy Using AGuIX®-Design Nanoparticles

et al. 2023

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“…The ultimate goal of glaucoma treatment is to protect the optic nerve and retinal ganglion cells. [4] Although nerve-nourishing drugs such as citicoline, nerve growth factor and mecobalamine have slowed the progression of glaucoma to some extent, their clinical efficacy remains limited. [5] FFXST is a proprietary Chinese medicine with the effect of promoting blood circulation and removing blood stasis, invigorating Qi and nourishing Yin, mainly composed of Panax notoginseng, Radix Astragali, Salvia miltiorrhiza and Radix Scrophulariae.…”

Section: Discussionmentioning

confidence: 99%

“…[3] The ultimate goal of glaucoma treatment is to protect the optic nerve and retinal ganglion cells, and reducing intraocular pressure and nerve nutrition are commonly used in the treatment of glaucoma. [4] Ophthalmic surgery to reduce intraocular pressure such as laser trabeculoplasty, trabeculectomy, non-penetrating glaucoma surgery and minimally invasive glaucoma surgery, combined with postoperative nutritional optic nerve therapy, can slow the progression of glaucoma. [5] Although drugs that nourish the optic nerve, such as Citicoline, have played a role in improving the prognosis of glaucoma, their clinical efficacy is still limited and the intervention of novel therapeutic strategies is urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of Fufang Xueshuantong Capsules in combination with conventional drugs in the treatment of glaucoma: A meta-analysis and trial sequential analysis

et al. 2023

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Background: Glaucoma is the leading cause of irreversible blindness worldwide. The aim of this study was to evaluate the efficacy and safety of Fufang Xueshuantong Capsules (FFXST) in combination with conventional drugs in the treatment of glaucoma using meta-analysis and trial sequential analysis (TSA). Methods: Clinical trials of FFXST for glaucoma were identified in 8 databases until November 2022, and studies were included for meta-analysis and trial sequential analysis. Results: In terms of efficacy endpoints, meta-analysis showed that the combination group of FFXST significantly improved clinical effective rate (RR 1.29, 95% CI 1.20–1.39, P < .00001), visual function (MD 0.04, 95% CI 0.04–0.05, P < .00001), light sensitivity (MD 6.07, 95% CI 4.63–7.51, P < .00001), end-systolic blood flow velocity (MD 2.68, 95% CI 2.19–3.16, P < .00001) and end-diastolic blood flow velocity (MD 2.07, 95% CI 1.86–2.28, P < .00001), and significantly reduced total gray-scale value (MD −64.38, 95% CI −69.08 to −59.68, P < .00001) and defect of visual field (MD −3.40, 95% CI −4.11 to −2.69, P < .00001) compared with the conventional regimen group, while the pulsatility index and resistance index were comparable. The TSA indicated that these benefits were conclusive. In terms of safety endpoints, meta-analysis demonstrated that total drug-related adverse events in the combination group of FFXST were comparable to those in the conventional regimen group, with TSA showing that more studies are needed to validate the current results. Conclusion: FFXST may be a safety and effective supplementary strategy for the treatment of glaucoma, which is worthy of further research.

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“…When these erythrocytes are phagocytosed by TAMs, TAMs are easily transformed into the pro-inflammatory, high-phagocytic M1 phenotype 96 . In this situation, the phagocytic activity of M1 TAMs towards tumors is reinforced 97 . Macrophage depletion attenuates the anti-tumor ability of RRx-001 in vivo , validating that the presence of tumoral-infiltrated macrophages is an indispensable condition for the antitumor activity of RRx-001 95 , 98 .…”

Section: Small Molecule Drugs Directly Targeting Immune Checkpointsmentioning

confidence: 99%

Development of small molecule drugs targeting immune checkpoints

Chen,

Zhao,

Liu

et al. 2024

Cancer Biol Med

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Immune checkpoint inhibitors (ICIs) are used to relieve and refuel anti-tumor immunity by blocking the interaction, transcription, and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints. Thousands of small molecule drugs or biological materials, especially antibody-based ICIs, are actively being studied and antibodies are currently widely used. Limitations, such as anti-tumor efficacy, poor membrane permeability, and unneglected tolerance issues of antibody-based ICIs, remain evident but are thought to be overcome by small molecule drugs. Recent structural studies have broadened the scope of candidate immune checkpoint molecules, as well as innovative chemical inhibitors. By way of comparison, small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features. Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions, including immune regulation, anti-angiogenesis, and cell cycle regulation. In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins, which will lay the foundation for further exploration.

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Macrophages in Glioblastoma Development and Therapy: A Double-Edged Sword

Cited by 11 publications

References 137 publications

Targeting Glioblastoma-Associated Macrophages for Photodynamic Therapy Using AGuIX®-Design Nanoparticles

Targeting Glioblastoma-Associated Macrophages for Photodynamic Therapy Using AGuIX®-Design Nanoparticles

Efficacy and safety of Fufang Xueshuantong Capsules in combination with conventional drugs in the treatment of glaucoma: A meta-analysis and trial sequential analysis

Development of small molecule drugs targeting immune checkpoints

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