Abstract:Background
Clinical studies have shown that the efficacy of programmed cell death receptor-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors on glioblastoma (GBM) is much lower than what is expected because of the low immunogenicity of GBM. Ferroptosis of cancer cells can induce the maturation of dendritic cells (DC cells) and increase the activity of T cell. The activated T cells release IFN-γ, which subsequently induces the ferroptosis of cancer cells. Thus, the aim of this paper is to… Show more
“…PD-L1 is related to HnPNPL. HnRNPL knockdown could inhibit the expression of PD-L1, thus producing increased IFN-γ, which triggers ferroptosis of CRPC cells by the STAT1/SLC7A11/GPX4 signaling axis Overcoming resistance to conventional cancer therapies TYRO3 inhibitors+ anti- PD1 [ 155 – 157 , 159 – 163 , 165 – 168 , 176 , 178 , 181 – 184 , 188 – 190 ] Fe3O4-siPD-L1@M-BV2 GW4869-meditated PD-L1-based exosomes zero-valent-iron nanoparticles (ZVI-NP) Specialized cell population TGF-β-producing Th3 cells TGF-β 1 could enhance ultrastructural variation in mitochondria with increased ROS and MDA Ferroptosis may obstruct immune tolerance GSH level and the lipid peroxidation Prohibiting TGF-β induced ferroptosis Low GSH level and enhanced lipid peroxidaton [ 193 – 201 ] TGF-β 2 could affect the expression of GPX4 and ACSL4 Fig. 2 Co-stimulatory, co-inhibitory and checkpoint pathways.…”
Section: Introductionmentioning
confidence: 99%
“…Glioblastoma (GBM) is an invasive intracranial malignant tumor [ 181 ]. Frustratingly, with long-term temozolomide (TMZ)-therapy in GBM patients, drug resistance ineluctably develops and the efficacy is remarkably attenuated or even eliminated [ 182 , 183 ].…”
Section: Introductionmentioning
confidence: 99%
“…Thereby, a novel GBM-targeting pharmaceutical delivering system, Fe 3 O 4 -siPD-L1@M-BV2, was constructed to facilitate ferroptosis for immunotherapy of drug-resistant GBM. A cascade of amplification between ferroptosis and immune activation was formed via the system, ultimately prohibiting tumor growth [ 181 ].…”
The term ferroptosis was put forward in 2012 and has been researched exponentially over the past few years. Ferroptosis is an unconventional pattern of iron-dependent programmed cell death, which belongs to a type of necrosis and is distinguished from apoptosis and autophagy. Actuated by iron-dependent phospholipid peroxidation, ferroptosis is modulated by various cellular metabolic and signaling pathways, including amino acid, lipid, iron, and mitochondrial metabolism. Notably, ferroptosis is associated with numerous diseases and plays a double-edged sword role. Particularly, metastasis-prone or highly-mutated tumor cells are sensitive to ferroptosis. Hence, inducing or prohibiting ferroptosis in tumor cells has vastly promising potential in treating drug-resistant cancers. Immunotolerant cancer cells are not sensitive to the traditional cell death pathway such as apoptosis and necroptosis, while ferroptosis plays a crucial role in mediating tumor and immune cells to antagonize immune tolerance, which has broad prospects in the clinical setting. Herein, we summarized the mechanisms and delineated the regulatory network of ferroptosis, emphasized its dual role in mediating immune tolerance, proposed its significant clinical benefits in the tumor immune microenvironment, and ultimately presented some provocative doubts. This review aims to provide practical guidelines and research directions for the clinical practice of ferroptosis in treating immune-resistant tumors.
“…PD-L1 is related to HnPNPL. HnRNPL knockdown could inhibit the expression of PD-L1, thus producing increased IFN-γ, which triggers ferroptosis of CRPC cells by the STAT1/SLC7A11/GPX4 signaling axis Overcoming resistance to conventional cancer therapies TYRO3 inhibitors+ anti- PD1 [ 155 – 157 , 159 – 163 , 165 – 168 , 176 , 178 , 181 – 184 , 188 – 190 ] Fe3O4-siPD-L1@M-BV2 GW4869-meditated PD-L1-based exosomes zero-valent-iron nanoparticles (ZVI-NP) Specialized cell population TGF-β-producing Th3 cells TGF-β 1 could enhance ultrastructural variation in mitochondria with increased ROS and MDA Ferroptosis may obstruct immune tolerance GSH level and the lipid peroxidation Prohibiting TGF-β induced ferroptosis Low GSH level and enhanced lipid peroxidaton [ 193 – 201 ] TGF-β 2 could affect the expression of GPX4 and ACSL4 Fig. 2 Co-stimulatory, co-inhibitory and checkpoint pathways.…”
Section: Introductionmentioning
confidence: 99%
“…Glioblastoma (GBM) is an invasive intracranial malignant tumor [ 181 ]. Frustratingly, with long-term temozolomide (TMZ)-therapy in GBM patients, drug resistance ineluctably develops and the efficacy is remarkably attenuated or even eliminated [ 182 , 183 ].…”
Section: Introductionmentioning
confidence: 99%
“…Thereby, a novel GBM-targeting pharmaceutical delivering system, Fe 3 O 4 -siPD-L1@M-BV2, was constructed to facilitate ferroptosis for immunotherapy of drug-resistant GBM. A cascade of amplification between ferroptosis and immune activation was formed via the system, ultimately prohibiting tumor growth [ 181 ].…”
The term ferroptosis was put forward in 2012 and has been researched exponentially over the past few years. Ferroptosis is an unconventional pattern of iron-dependent programmed cell death, which belongs to a type of necrosis and is distinguished from apoptosis and autophagy. Actuated by iron-dependent phospholipid peroxidation, ferroptosis is modulated by various cellular metabolic and signaling pathways, including amino acid, lipid, iron, and mitochondrial metabolism. Notably, ferroptosis is associated with numerous diseases and plays a double-edged sword role. Particularly, metastasis-prone or highly-mutated tumor cells are sensitive to ferroptosis. Hence, inducing or prohibiting ferroptosis in tumor cells has vastly promising potential in treating drug-resistant cancers. Immunotolerant cancer cells are not sensitive to the traditional cell death pathway such as apoptosis and necroptosis, while ferroptosis plays a crucial role in mediating tumor and immune cells to antagonize immune tolerance, which has broad prospects in the clinical setting. Herein, we summarized the mechanisms and delineated the regulatory network of ferroptosis, emphasized its dual role in mediating immune tolerance, proposed its significant clinical benefits in the tumor immune microenvironment, and ultimately presented some provocative doubts. This review aims to provide practical guidelines and research directions for the clinical practice of ferroptosis in treating immune-resistant tumors.
“…Fe 3 O 4 -siPD-L1@M- BV2 increased Fe 2+ accumulation in mouse GBM-resistant cells and significantly decreases the expression of programmed death-ligand 1 (PD-L1). Fe 3 O 4 -siPD-L1@M- BV2 also increases the ratio of effector T cells to regulatory T cells in drug-resistant GBM ( 111 ). Amentoflavone (AF) can not only induce autophagy in glioma cells by regulating the AMPK/mTOR pathway but is also associated with ferroptosis in gliomas.…”
Section: Ferroptosis In Glioma Treatmentmentioning
Glioma is the most common malignant tumor of the central nervous system and resistance is easily developed to chemotherapy drugs during the treatment process, resulting in high mortality and short survival in glioma patients. Novel therapeutic approaches are urgently needed to improve the therapeutic efficacy of chemotherapeutic drugs and to improve the prognosis of patients with glioma. Ferroptosis is a novel regulatory cell death mechanism that plays a key role in cancer, neurodegenerative diseases, and other diseases. Studies have found that ferroptosis-related regulators are closely related to the survival of patients with glioma, and induction of ferroptosis can improve glioma resistance to chemotherapy drugs. Therefore, induction of tumor cell ferroptosis may be an effective therapeutic strategy for glioma. This review summarizes the relevant mechanisms of ferroptosis, systematically summarizes the key role of ferroptosis in the treatment of glioma and outlines the relationship between ferroptosis-related ncRNAs and the progression of glioma.
“…Tf is an 80 k Da glycoprotein found in plasma and represents an essential growth factor for cell proliferation ( Ratan, 2020 ; Zhao et al, 2022 ). However, Tf is not present in all brain regions but mainly in oligodendrocytes, cerebrospinal fluid and brain capillary endothelial cells ( Libby et al, 2021 ; Liu et al, 2022 ). Regulation of Tf is accomplished through a specific set of proteins that regulate the concentration of iron in tumor cells ( Li et al, 2014 ; Yang et al, 2022 ).…”
Ferroptosis is a newly identified form of cell death that differs from autophagy, apoptosis and necrosis, and its molecular characteristics include iron-dependent lipid reactive oxygen species accumulation, mitochondrial morphology changes, and membrane permeability damage. These characteristics are closely related to various human diseases, especially tumors of the nervous system. Glioblastoma is the most common primary malignant tumor of the adult central nervous system, and the 5-year survival rate is only 4%–5%. This study reviewed the role and mechanism of ferroptosis in glioblastoma and the research status and progress on ferroptosis as a potential therapeutic target. The mechanism of ferroptosis is related to the intracellular iron metabolism level, lipid peroxide content and glutathione peroxidase 4 activity. It is worth exploring how ferroptosis can be applied in disease treatment; however, the relation between ferroptosis and other apoptosis methods is poorly understood and methods of applying ferroptosis to drug-resistant tumors are insufficient. Ferroptosis is a promising therapeutic target for glioblastoma. In-depth studies of its mechanism of action in glioblastoma and applications for clinical treatment are expected to provide insights for glioblastoma patients.
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