GPX4 and FSP1, key ferroptosis regulators, are critical for T cell functions and CAR-T antitumor activity DOI Creative Commons
Małgorzata Bajor, Marta Kłopotowska, Iwona Baranowska

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 30, 2024

Abstract Induction of ferroptosis, an iron-dependent form regulated cell death, holds promise as a strategy to overcome tumor resistance conventional therapies and enhance immunotherapy responses. However, while the susceptibility cells ferroptosis is extensively studied, limited data exists on vulnerability immune disturbed iron balance lipid peroxidation. Here, we found that T stimulation rewires redox homeostasis by increasing levels reactive oxygen species labile promotes peroxidation cells’ ferroptosis. Upon stimulation, detected substantial changes in ferroptosis-suppressive proteins, including GPX4 decrease increase FSP1, phenomenon never described before. Subsequently, identified master regulator orchestrating T/CAR-T sensitivity demonstrated inhibitors impair functions. Surprisingly, observed FSP1 regulates antitumor activity independently its function. Specifically, inhibition decreased oxidative phosphorylation mitochondrial ATP production, reduced amount perforin cytokines produced cells, suppressed their proliferation. Altogether, our study for first time indicates key regulators are critical cytotoxic potential cells. From also emerges novel metabolic which profoundly affects phosphorylation. Our findings not only significant understand vulnerabilities but may hold particular significance from standpoint therapeutic development. In context results, future anticancer should be carefully designed selectively induce without impeding efficacy.

Language: Английский

Emerging targets in lipid metabolism for cancer therapy DOI Creative Commons
Alexander R. Terry, Nissim Hay

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(6), P. 537 - 551

Published: May 17, 2024

Cancer cells perturb lipid metabolic pathways for a variety of pro-tumorigenic functions, and deregulated cellular metabolism is hallmark cancer cells. Although alterations in have been appreciated over 20 years, there are no FDA-approved treatments that target lipid-related pathways. Recent advances pertaining to cell fatty acid synthesis (FAS), desaturation, uptake, microenvironmental dietary lipids, tumor-infiltrating immune illuminated promising clinical applications targeting metabolism. This review highlights emerging targets tumor may soon impact treatment.

Language: Английский

Citations

22
Magnolia kobus DC. suppresses neointimal hyperplasia by regulating ferroptosis and VSMC phenotypic switching in a carotid artery ligation mouse model DOI Creative Commons
Jong Min Kim, Yiseul Kim,

Hyun-Jin Na

et al.

Chinese Medicine, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 3, 2025

Abstract Background Magnolia kobus DC (MO), as a plant medicine, has been reported to have various physiological activities, including neuroprotective, anti-inflammatory, and anti-diabetic effects. However, vascular protective effects of MO remain incompletely understood. In this study, we evaluated the effect against ferroptosis in carotid artery ligation (CAL)-induced neointimal hyperplasia mouse model aortic thoracic smooth muscle A7r5 cells. Methods This study was conducted estimate by systematically measuring histopathological analysis western blot CAL animal model. vitro were estimating cell viability, reactive oxygen species (ROS) content, glutathione (GSH) levels, lipid peroxidation, mitochondrial morphological change, proliferation, migration, analysis, qRT-PCR erastin (Era)-induced Results intake significantly improved formation, inhibited (VSMC) phenotypes, ameliorated antioxidant system tissues. addition, treatment effectively Era-induced ferroptotic cytotoxicity, cellular death, ROS production, migration status. also suppressed proliferation considerably regulated abnormal mechanisms related changes, VSMC phenotype switching, scavenging Conclusion potential for use functional food supplement, nutraceutical, or medicinal food, with on health regulating phenotypic switching.

Language: Английский

Citations

2
Ferroptosis: CD8+T cells’ blade to destroy tumor cells or poison for self-destruction DOI Creative Commons
Yuan Liang, Yixin Zhao, Zhili Qi

et al.

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

Citations

2
Ferroptosis and the tumor microenvironment DOI Creative Commons
Kaisa Cui, Kang Wang, Zhaohui Huang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Nov. 30, 2024

Abstract Ferroptosis is a type of regulated cell death characterized by its non-apoptotic, iron-dependent and oxidative nature. Since discovery in 2012, extensive research has demonstrated pivotal roles tumorigenesis, metastasis cancer therapy. The tumor microenvironment (TME) complex ecosystem comprising cells, non-cancer extracellular matrix, metabolites cytokines. Recent studies have underscored new paradigm which cells the TME, such as immune stromal also play significant regulating progression therapeutic resistance typically through complicated crosstalk with cells. Notably, this TME were partially mediated ferrotopsis-related mechanisms. This review provides comprehensive systematic summary current findings concerning ferroptosis how ferroptosis-mediated reprogramming impacts progression. Additionally, outlines various ferroptosis-related strategies aimed at targeting TME.

Language: Английский

Citations

10
Ferroptosis of T cell in inflammation and tumour immunity DOI Creative Commons
Xueli Xia, Haisheng Wu, Yuxuan Chen

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

Ferroptosis is an innovative concept defined as a distinct programmed cell death mode regulated by iron-dependent lipid peroxidation accumulation. This process governed numerous energy metabolites such fatty acids, amino acids and glucose, well iron homeostasis. In recent years, increasing studies have been devoted to the crucial effects of ferroptosis in immune cells during pathogenesis diseases infections, tumours autoimmune disorders. review summarises latest advancements T-cell ferroptosis, addresses key components mechanism T inflammatory conditions tumour progression, highlights potential target for treating related diseases. KEY POINTS: Ferroptosis-related mechanisms significantly affect biology CD4+ subsets are further involved Crosstalk between CD8+ induces microenvironment. Glutathione peroxidase 4 loss promotes regulatory enhance anti-tumour immunity.

Language: Английский

Citations

1
Ferroptosis meets inflammation: a new frontier in cancer therapy DOI
Hu Liu,

Hui Xue,

Qian Guo

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217696 - 217696

Published: April 1, 2025

Language: Английский

Citations

1
Targeting SLC7A11-mediated cysteine metabolism for the treatment of trastuzumab resistant HER2 positive breast cancer DOI Open Access
Yijia Hua, Ningjun Duan, Chunxiao Sun

et al.

Published: Feb. 5, 2025

Trastuzumab resistance remains a challenge for HER2 positive breast cancer treatment. Targeting metabolic reprogramming would provide novel insights therapeutic strategies. Here, we integrated metabolomics, transcriptomics and epigenomics data of trastuzumab sensitive primary resistant to identify alterations. Aberrant cysteine metabolism was discovered in at both circulating intracellular levels. The inhibition SLC7A11 starvation could synergize with induce ferroptosis. Mechanistically, increased H3K4me3 decreased DNA methylation enhanced transcription cystine uptake cancer. regulation epigenetic modifications modulated ferroptosis sensitivity. These results revealed an innovative approach overcoming by targeting specific amino acid metabolism.

Language: Английский

Citations

0
Targeting SLC7A11-mediated cysteine metabolism for the treatment of trastuzumab resistant HER2 positive breast cancer DOI Open Access
Yijia Hua, Ningjun Duan, Chunxiao Sun

et al.

Published: Feb. 5, 2025

Trastuzumab resistance remains a challenge for HER2 positive breast cancer treatment. Targeting metabolic reprogramming would provide novel insights therapeutic strategies. Here, we integrated metabolomics, transcriptomics and epigenomics data of trastuzumab sensitive primary resistant to identify alterations. Aberrant cysteine metabolism was discovered in at both circulating intracellular levels. The inhibition SLC7A11 starvation could synergize with induce ferroptosis. Mechanistically, increased H3K4me3 decreased DNA methylation enhanced transcription cystine uptake cancer. regulation epigenetic modifications modulated ferroptosis sensitivity. These results revealed an innovative approach overcoming by targeting specific amino acid metabolism.

Language: Английский

Citations

0
Targeting amino acid metabolism to inhibit gastric cancer progression and promote anti-tumor immunity: a review DOI Creative Commons

Yuchun Jiang,

Tao Qing,

Xuehan Qiao

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 13, 2025

The incidence of gastric cancer remains high and poses a serious threat to human health. Recent comprehensive investigations into amino acid metabolism immune system components within the tumor microenvironment have elucidated functional interactions between cells, metabolism. This study reviews characteristics in cancer, with particular focus on methionine, cysteine, glutamic acid, serine, taurine, other acids. It discusses relationship these metabolic processes, development, body’s anti-tumor immunity, analyzes importance targeting for chemotherapy immunotherapy.

Language: Английский

Citations

0
New insights into T cell metabolism in liver cancer: from mechanism to therapy DOI Creative Commons
Jie Xiao, Ting Liu, Fanxin Zeng

et al.

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

Published: March 23, 2025

Abstract Liver cancer is the sixth most common worldwide and third cause of mortality. The development progression liver metastases a multifaceted process involving numerous metabolic pathways. T cells have protective role in defense against cancer, manipulating pathways can alter their antitumor activity. Furthermore, cell nutrition competition lead to dysfunction through various molecular mechanisms. Some nanomaterials drugs improve metabolism promote anti-liver function cells. This review discusses current literature regarding changes targeted therapy for cancer. promise challenges studying target treating are also addressed. Targeting promising approach

Language: Английский

Citations

0