IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Янв. 16, 2025

Abstract Keloid is benign skin tumor, and their curing relatively difficult due to the unclear mechanism of formation. Inducing ferroptosis keloid fibroblasts (KFs) may become a new method for treating keloid. Here, we discover interferon (IFN)γ could induce KFs through inhibiting SPOC domain-containing protein 1 (SPOCD1), serving as mode action CD8 + T cell (CTL)-mediated killing. Mechanistically, IFNγ deficiency in combination with reduced DNMT3A increase expression SPOCD1, thereby promoting KFs’ proliferation its ferroptosis. Moreover, SPOCD1 attenuates progression extracellular matrix (ECM) deposition. Reducing simultaneously can positive rate reactive oxygen species (ROS) promote mitochondrial shrinkage. Ex-vivo explant culture has also confirmed that reduction helps reduce KFs, inhibit angiogenesis scars, thus Thus, signaling paired natural CTLs. Targeting pathway potential anti-keloid approach.

Язык: Английский

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Immunometabolism of ferroptosis in the tumor microenvironment

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Авг. 12, 2024

Ferroptosis is an iron-dependent form of cell death that results from excess lipid peroxidation in cellular membranes. Within the last decade, physiological and pathological roles for ferroptosis have been uncovered autoimmune diseases, inflammatory conditions, infection, cancer biology. Excitingly, metabolism may be targeted to induce by cancers are resistant other forms death. sensitivity regulated oxidative stress, metabolism, iron which all influenced tumor microenvironment (TME). Whereas some types shown adapt these stressors, it not clear how immune cells regulate their sensitivities ferroptosis. In this review, we discuss mechanisms different subsets, influences infiltrate TME, interactions can determine epithelial-to-mesenchymal transition (EMT) metastasis. While much focus has placed on inducing cells, important considerations ferroptosis-modulating strategies impact anti-tumor immunity. From perspective, also promising immunotherapies field challenges associated with targeting specific populations.

Язык: Английский

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The role of ferroptosis in colorectal cancer and its potential synergy with immunotherapy

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 9, 2025

Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies worldwide. Recently, ferroptosis, a novel form regulated cell death characterized by iron dependency lipid peroxidation, has garnered significant attention from researchers. The mechanisms underlying including intracellular levels, antioxidant system regulation, offer new insights into treatment strategies. This study aims to explore emerging role ferroptosis in context immunotherapy for CRC, highlighting its potential clinical applications. We employed comprehensive review current literature elucidate biological relationship with interplay between immunotherapy. Ferroptosis reshapes tumor microenvironment (TME) regulating metabolism, systems, significantly enhancing efficacy immune checkpoint inhibitors (ICIs). Meanwhile, traditional Chinese medicine therapies promote antitumor immunity modulating TME inducing ferroptosis. Additionally, advances nanotechnology have facilitated precise therapy enabling targeted delivery inducers or immunomodulators, transforming "cold" tumors "hot" further boosting ICI efficacy. comprehensively reviews latest developments immunotherapy, medicine, importance ferroptosis-related biomarkers personalized treatment. In summary, offers promising strategy overcome CRC resistance enhance efficacy, warranting investigation translational application.

Язык: Английский

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Regulation of Ferroptosis in Cancer and Immune Cells

Immune Network, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 1, 2025

Ferroptosis, an iron-dependent form of regulated cell death, is driven by lipid peroxidation and shaped metabolic antioxidant pathways. In immune cells, ferroptosis susceptibility varies types, composition, demands, influencing responses in cancer, infections, autoimmune diseases. Therapeutically, targeting holds promise cancer immunotherapy enhancing antitumor immunity or inhibiting immunosuppressive cells. This review highlights the pathways underlying ferroptosis, its regulation dual role tumor progression immunity, context-dependent therapeutic implications for optimizing treatment.

Язык: Английский

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HDAC3: A Multifaceted Modulator in Immunotherapy Sensitization

Vaccines, Год журнала: 2025, Номер 13(2), С. 182 - 182

Опубликована: Фев. 13, 2025

Histone deacetylase 3 (HDAC3) has emerged as a critical epigenetic regulator in tumor progression and immune modulation, positioning it promising target for enhancing cancer immunotherapy. This work comprehensively explores HDAC3's multifaceted roles, focusing on its regulation of key immune-modulatory pathways such cGAS-STING, ferroptosis, the Nrf2/HO-1 axis. These are central to evasion, antigen presentation, cell activation. Additionally, distinct effects HDAC3 various types-including role T activation, restoring NK cytotoxicity, promoting dendritic maturation, modulating macrophage polarization-are thoroughly examined. findings underscore capacity reshape microenvironment, converting immunologically "cold tumors" into "hot thereby increasing their responsiveness The therapeutic potential inhibitors is highlighted, both standalone agents combination with checkpoint inhibitors, overcome resistance improve treatment efficacy. Innovative strategies, development selective advanced nano-delivery systems, integration photodynamic or photothermal therapies, proposed enhance precision minimize toxicity. By addressing challenges toxicity, patient heterogeneity, mechanisms, this study provides forward-looking perspective clinical application inhibitors. It highlights significant personalized immunotherapy, paving way more effective treatments improved outcomes patients.

Язык: Английский

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Simvastatin inhibits PD-L1 via ILF3 to induce ferroptosis in gastric cancer cells

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Март 26, 2025

Abstract The treatment of gastric cancer remains challenging, with immunotherapy serving as a critical component the holistic approach to its treatment. results this study indicated that statins could decrease serum levels interleukin-enhancing binding factor 3 (ILF3) and programmed cell death ligand 1(PD-L1) in GC patients improve their prognosis. Functional experiments demonstrated simvastatin induced ferroptosis by inhibiting ILF3 cells enhanced killing effect activated CD8 + T on cells. CUT&Tag assay revealed that, mechanistically, inhibited expression reducing acetylation level at residue site H3K14 ILF3. Next-generation sequencing Kyoto Encyclopedia Genes Genomes analysis regulated PD-L1 through DEPTOR/mTOR signaling pathway. Overall, while promoting activation augment antitumor immune responses, thereby facilitating synergistic immunotherapy.

Язык: Английский

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Enzymatic Oxidants, Antioxidants, and Inflammatory Bowel Disease

Applied Biosciences, Год журнала: 2025, Номер 4(2), С. 19 - 19

Опубликована: Апрель 1, 2025

The role of oxidants and antioxidants in inflammatory bowel disease (IBD) has been actively explored since the early 1980s, starting with respiratory burst neutrophils ischemia pathology. Since that time, enzymatic components contributing to pool reactive oxygen species, including superoxide, H2O2, lipid hydroperoxides, counteracting antioxidants—catalase, glutathione peroxidases (Gpx), peroxiredoxins (PRDX), superoxide dismutases, others—have fleshed out. My perspective on IBD is from balance or imbalance oxidant sources process. I will present evidence involvement antioxidant processes based, as much possible, my experiences Gpxs. This be discussed terms both immune system local systems. As Gpxs are generally selenium-dependent, possible deficiencies selenium uptake active impact Gpx expression explored. more recently introduced ferroptosis, an iron-dependent peroxidation-based pathological process, reviewed for its IBD.

Язык: Английский

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Elucidation of the mechanism Underlying the promotion of ferroptosis and enhanced antitumor immunity by citrus polymethoxyflavones in CRC cells

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 11, 2025

Background Colon cancer is a prevalent condition with high mortality rate on global scale. Research has indicated that Citrus polymethoxyflavones (PMFs), class of flavonoids found in Citrus, possess the potential to demonstrate anti-tumor efficacy. Ferroptosis form cell death dependent iron accumulation and lipid peroxidation. Immunotherapy one most commonly used modalities clinical setting. Consequently, studies pharmacodynamic mechanism determine whether it can modulate tumor immunity through ferroptosis provide new ideas for treatment colon cancer. Purpose The objective this study ascertain inhibits PD-L1 promotes among patients Methods inhibitory effect PMFs was proved by vitro experiment vivo model. In addition, occurrence detected measuring key indicators. Bioinformatics analysis then performed identify crossover genes polymethoxylflavonoids, cancer, ferroptosis. Finally, were identified immunocorrelation including WB, Q-PCR flow cytometry. These experiments designed reveal mechanisms immunity. Results proliferation growth transplanted mice showed had change index promoted ferroptosis, followed WB detection NOX4 TIMP1 , screened bioinformatics, inhibited down-regulating thus affecting Flow cytometry CD4 + T expression increased CD8 decreased after treatment, suggesting activated. Conclusion It conceivable immune microenvironment may be subject regulation during inhibition PMFs. ferroptosis-related gene been observed regulate thereby promoting However, further investigation required underlyingprecise mechanisms.

Язык: Английский

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Analysis of CDO1, PITX2, and CDH13 Gene Methylation in Early Endometrial Cancer for Prediction of Medical Treatment Outcomes

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(9), С. 4892 - 4892

Опубликована: Апрель 30, 2024

An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical hyperplasia (AEH), undergoing organ-preserving treatment, was conducted. Objective the study: To determine CDO1, PITX2, and CDH13 gene methylation levels in early specimens obtained before treatment adequate response insufficient to hormonal treatment. Materials methods: A total 41 during diagnostic uterine curettage women EC (n = 28) AEH 13), willing preserve reproductive function, were studied; 18 G1 from peri- postmenopausal (comparison group) included study. The control group healthy by for missed abortion and/or intrauterine adhesions. Methylation analyzed using modified MS-HRM method. Results: All 13 had a complete (CR) medical In 28), 14 (EC CR did not non-CR group). It found that all groups statistically significant differences CDO1 compared (p < 0.001) except 0.21). p-value difference between <0.001. PITX2 also significantly different 0.001), For groups, 0.43. levels, comparison 0.005). When comparing group, this simultaneous assessment genes allowed an accurate distinction (AUC 0.96). Conclusion: (IA G1), scheduled can predict outcome.

Язык: Английский

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Targeting Ferroptosis as an Advance Strategy in Cancer Therapy

Antioxidants and Redox Signaling, Год журнала: 2024, Номер 41(10-12), С. 616 - 636

Опубликована: Июль 3, 2024

This study innovates by systematically integrating the molecular mechanisms of iron death and its application in cancer therapy. By deeply analyzing interaction between tumor microenvironment, provides a new theoretical basis for treatment directions developing more effective strategies. In addition, points to critical issues barriers that need be addressed future research, providing valuable insights into use clinical translation.

Язык: Английский

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