Ferroptosis: CD8+T cells’ blade to destroy tumor cells or poison for self-destruction

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 1, 2025

Abstract Ferroptosis represents an emerging, iron-dependent form of cell death driven by lipid peroxidation. In recent years, it has garnered significant attention in the realm cancer immunotherapy, particularly studies involving immune checkpoint inhibitors. This not only enhances our comprehension tumor microenvironment but is also considered a promising therapeutic strategy to address resistance, investigate activation mechanisms, and facilitate development vaccines. The combination immunotherapy with ferroptosis provides innovative targets fresh perspectives for advancing treatment. Nevertheless, cells appear possess wider array evasion strategies compared CD8 + T cells, which have been conclusively shown be more vulnerable ferroptosis. Furthermore, TME can create favorable environment survival invasion. Under this premise, both inducing inhibiting will impact antitumor immunity some extent, even make final result run counter purpose. paper systematically elucidates dual-edged sword role process briefly outlining complexity within TME. It explores potential side effects associated ferroptosis-inducing therapies critically considers combined application ferroptosis-based ICIs. highlights current challenges faced approach points out future directions development.

Language: Английский

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The potential roles of HIF-1α in epithelial-mesenchymal transition and ferroptosis in tumor cells

Cellular Signalling, Journal Year: 2024, Volume and Issue: 122, P. 111345 - 111345

Published: Aug. 10, 2024

In tumors, the rapid proliferation of cells and imperfect blood supply system lead to hypoxia, which can regulate adaptation tumor hypoxic environment through hypoxia-inducible factor-1α (HIF-1α) promote development in multiple ways. Recent studies have found that epithelial-mesenchymal transition (EMT) ferroptosis play important roles progression cells. The activation HIF-1α is considered a key factor inducing EMT When activated, it EMT-related genes, causing gradually lose their epithelial characteristics acquire more invasive mesenchymal traits. occurrence allows better adapt changes surrounding tissue, enhancing migratory capabilities, thus promoting progression. At same time, also plays crucial regulatory role environment, may affect processes such as iron metabolism oxidative stress responses, This article briefly reviews dual cells, helping gain deeper understanding pathways providing new perspective for pathogenesis tumors. regulation become an strategy future therapy.

Language: Английский

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Comprehensive review of amino acid transporters as therapeutic targets

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 260, P. 129646 - 129646

Published: Jan. 23, 2024

Language: Английский

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Boosting Ferroptosis and immunotherapy for Colorectal Cancer by Lactate‐Related Metabolic Reprogramming

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(52)

Published: Aug. 27, 2024

Abstract As the presence of anaerobic metabolism glucose, solid tumors characteristically display higher levels lactate production, which attenuate ferroptosis therapy and subsequent anti‐tumor immune response. Herein, hyaluronic acid (HA)‐modified oxidase (LOX)‐loaded nanoscale metal organic frameworks (MOFs), termed as FCS@LOX@HA (FCSLH) is constructed, achieving tumor‐targeted metabolic combined chemo‐dynamic (CDT). Notably, high LOX‐loading capacity MOFs achieved by adjusting Fe/Cu ratio. Upon internalization cancer cells, FCS reacted with local glutathione (GSH) to release ions for CDT. Meanwhile, LOX catalyzed endogenous pyruvate accompanied a H 2 O ; while latter can enhance MOFs‐mediated CDT effect. Additionally, exhaustion impair antioxidant system inhibiting HIF‐1α/SLC1A1 pathway, resulting in accumulation lipid peroxidation, occurs immunogenic cell death. Furthermore, within tumor‐associated macrophages (TAMs) inhibit M2 macrophage polarization suppressing NF‐κB/HIF‐1α thereby augmenting The vivo studies demonstrated that cooperating PD‐L1 antibodies achieve excellent therapeutic efficacy. Taken together, FCSLH amplify ferroptosis‐mediated response through simultaneous dysfunction cells TAMs, provides novel insight integrating programmed immunotherapy.

Language: Английский

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Novel Covalent Probe Selectively Targeting Glutathione Peroxidase 4 In Vivo: Potential Applications in Pancreatic Cancer Therapy

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(3), P. 1872 - 1887

Published: Jan. 24, 2024

Glutathione peroxidase 4 (GPX4) emerges as a promising target for the treatment of therapy-resistant cancer through ferroptosis. Thus, there is broad interest in development GPX4 inhibitors. However, majority reported inhibitors utilize chloroacetamide reactive electrophilic warhead, and selectivity pharmacokinetic properties still need to be improved. Herein, we developed compound library based on novel sulfonyl ynamide, executed phenotypic screening against pancreatic cell lines. Notably, one A16 exhibiting potent toxicity was identified. Further chemical proteomics investigations have demonstrated that specifically targets under both situ vivo conditions, inducing Importantly, exhibited superior potency compared inhibitors, ML210 ML162. This provides structural diversity tool probes unraveling fundamental biology exploring therapeutic potential via ferroptosis induction.

Language: Английский

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