Targeting lipid metabolism in regulatory T cells for enhancing cancer immunotherapy

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер unknown, С. 189259 - 189259

Опубликована: Янв. 1, 2025

As immunosuppressive cells, Regulatory T cells (Tregs) exert their influence on tumor immune escape within the microenvironment (TME) by effectively suppressing activity of other thereby significantly impeding anti-tumor response. In recent years, metabolic characteristics Tregs have become a focus research, especially important role lipid metabolism in maintaining function Tregs. Consequently, targeted interventions aimed at modulating been recognized as an innovative and promising approach to enhance effectiveness immunotherapy. This review presents comprehensive overview pivotal regulating Tregs, with specific targeting augment responses. Furthermore, we discuss potential opportunities challenges associated this strategy, aiming provide novel insights for enhancing efficacy cancer

Язык: Английский

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Metabolic Reprogramming in Prostate Cancer: The Roles of HOXB13 and FASN in Tumor Progression and Therapy

Опубликована: Янв. 14, 2025

Metabolic reprogramming, particularly lipid metabolism, is a hallmark of cancer progression and critical vulnerability in prostate (PCa). Two pivotal studies, one by Lu et al. the other Dairo al., have illuminated roles HOXB13, transcriptional regulator, fatty acid synthase (FASN), key enzyme biosynthesis, metabolic dysregulation PCa. The study highlights HOXB13’s role androgen receptor (AR)-independent PCa, where it regulates metabolism via epigenetic mechanisms involving histone deacetylase HDAC3. A G84E mutation HOXB13 disrupts this regulation, leading to increased synthesis pro-metastatic phenotype. demonstrates that FASN hypomethylation, coupled with expression, drives biosynthesis for tumor growth. Both studies establish link between mutations dysregulation, underscoring their interplay PCa biology. Therapeutically, pharmacological inhibition mitigates aggressive features HOXB13-deficient or mutant highlighting as promising target. Despite strengths, including robust methodologies, limitations include reliance on preclinical models need broader patient diversity. These collectively emphasize potential interventions precision medicine paving way novel therapies targeting patients specific genetic profiles.

Язык: Английский

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Plant polyphenols as natural bioactives for alleviating lipid metabolism disorder: Mechanisms and application challenges

Food Research International, Год журнала: 2025, Номер 203, С. 115682 - 115682

Опубликована: Янв. 16, 2025

Язык: Английский

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Lipid metabolic reprograming: the unsung hero in breast cancer progression and tumor microenvironment

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Март 3, 2025

Aberrant lipid metabolism is a well-recognized hallmark of cancer. Notably, breast cancer (BC) arises from lipid-rich microenvironment and depends significantly on metabolic reprogramming to fulfill its developmental requirements. In this review, we revisit the pivotal role in BC, underscoring impact progression tumor microenvironment. Firstly, delineate overall landscape highlighting roles patient prognosis. Given that lipids can also act as signaling molecules, next describe exchanges between BC cells other cellular components Additionally, summarize therapeutic potential targeting aspects processes, lipid-related transcription factors immunotherapy BC. Finally, discuss possibilities problems associated with clinical applications lipid‑targeted therapy propose new research directions advances spatiotemporal multi-omics.

Язык: Английский

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Microenvironmental arginine restriction sensitizes pancreatic cancers to polyunsaturated fatty acids by suppression of lipid synthesis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

Nutrient limitation is a characteristic feature of poorly perfused tumors. In contrast to well-perfused tissues, nutrient deficits in tumors perturb cellular metabolic activity, which imposes constraints on cancer cells. The created by the tumor microenvironment can lead vulnerabilities cancers. Identifying and that arise cancers provide new insight into biology identify promising antineoplastic targets. To how constrains metabolism pancreatic tumors, we challenged cells with microenvironmental levels analyzed changes cell metabolism. We found arginine perturbs saturated monounsaturated fatty acid synthesis suppressing lipogenic transcription factor SREBP1. Synthesis these acids critical for maintaining balance saturated, monounsaturated, polyunsaturated membranes. As consequence synthesis, are unable maintain lipid homeostasis when exposed acids, leading death ferroptosis. sum, restriction cancers, renders vulnerable polyunsaturated-enriched fat sources.

Язык: Английский

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Novel network construction algorithm for the study of similarity and differential mechanisms between different clinical treatments: from key metabolites to the related genes for personalized therapy of breast cancer

Analytical Biochemistry, Год журнала: 2025, Номер unknown, С. 115852 - 115852

Опубликована: Март 1, 2025

Язык: Английский

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Pan-cancer analysis reveals MTTP as a prognostic and immunotherapeutic biomarker in human tumors

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 27, 2025

Introduction Microsomal triglyceride transfer protein (MTTP) is an essential lipid for the synthesis and secretion of very low density lipoprotein (VLDL) in hepatocytes chylomicrons (CM) intestinal cells. Further researches have revealed that MTTP exerted its functions a variety tissues beyond liver intestine, including heart, neural antigen-presenting Dysregulation expression can lead to many diseases, such as metabolism disorders, insulin resistance cardiovascular diseases. Despite importance, research on cancer limited, with no comprehensive pan-cancer studies available. Methods was explored TIMER 2.0 Sangerbox databases. The pathological stages survival analysis were analyzed via GEPIA Kaplan Meier plotter. gene mutations by cBioPortal database. immune landscape tumor microenvironment(TME) using single-cell sequencing. Based RNA-seq data TCGA, we constructed GSEA enrichment MTTP. We identified pro-tumor anti-ferroptosis gastric (GC) cells vitro vivo experiments, effect TME ferroptosis Results elevated at least 1/3 tumors. High associated poor prognosis most levels significantly correlated three scores (immune, stromal, extimate) checkpoints half types. Single cell sequencing showed mainly expressed macrophages, especially microglia. increased GC knockdown limited proliferation, migration invasion abilities cells, accompanied sensitivity ferroptosis. In addition, analyzing genes single level, found macrophages may be involved process GC. Conclusions Our study emphasizes promising prognostic immunotherapeutic biomarker infiltration diverse regulates providing potential target immunotherapy.

Язык: Английский

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Progress in applications of ambient ionization mass spectrometry for lipids identification

Chinese Journal of Chromatography, Год журнала: 2025, Номер 43(1), С. 22 - 32

Опубликована: Янв. 1, 2025

Lipids are indispensable components of living organisms and play pivotal roles in cell-membrane fluidity, energy provision, neurotransmitter transmission transport. can act as potential biomarkers diseases given their abilities to indicate cell-growth status. For example, the lipid-metabolism processes cancer cells distinct from those normal owing rapid proliferation adaptation ever-changing biological environments. As a result, ability rapidly detect, identify, monitor lipid is critical for tracking life-related may enhance diagnosis treatment efficacy. Mass spectrometry (MS) regarded be among most efficient methods directly obtaining molecular-structural information, distinctly advantageous identifying lipids. Recent years have witnessed emergence ambient mass (AMS), which enables direct analyte sampling ionization without need sample preprocessing. These characteristics endow AMS with special advantages monitoring Furthermore, ongoing development soft technologies has led widespread use detection complex diverse molecules. Electrospray (ESI) gentle method that used detect medium-to-high-polarity compounds provide detailed chemical information lipids by producing fine mist charged droplets liquid sample. Consequently, series ESI-based been developed fabricating different systems capable detecting simple manner. desorption electrospray (DESI) extensively employed techniques, wide range samples, including solids, liquids, gases. DESI involves spraying solvent onto surface sample, after desorbed, ionized, generated ions transferred detector spectrometer via gas plume. easily precisely regulate space, thereby offering highly effective approach in-situ tissue samples. Additionally, single-cell analysis limited small cell volumes, cellular matrices, minimal absolute amounts analyte. Common single include flow cytometry fluorescence microscopy, both require fluorescent labeling specific target molecules, limits selectivity reproducibility some extent. emerged more-effective high sensitivity, low consumption, throughput, multiple-detection capabilities. Moreover, diversity poses significant challenge determining structural details. Therefore, AMS-based augmented chemical-treatment more-comprehensive gas-phase dissociation techniques discriminate between C=C-bond isomers sn-positions. Strategies involve chemically modifying C=C bonds prior MS also employed. Paternò-Büchi (P-B) photochemical reaction oxidizes unsaturated form oxetane structures, epoxidized corresponding oxaziridines, N-H aziridination converts into aziridines, 1ΔO2 ene adds an OOH group bond. In this review, we discuss various environmental over past five years, emphasis on typical strategies analyze structures. Obtaining high-coverage, high-sensitivity lipid-detection platform based remains challenging requires further in-depth studies despite improvements MS-based techniques.

Язык: Английский

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Efficient Discovery of Robust Prognostic Biomarkers and Signatures in Solid Tumors

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217502 - 217502

Опубликована: Янв. 1, 2025

Язык: Английский

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ONC201-Derived Tetrahydropyridopyrimidindiones as Powerful ClpP Protease Activators to Tackle Diffuse Midline Glioma

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Pediatric diffuse intrinsic pontine glioma (DIPG), classified under midline glioma, is a deadly tumor, with no effective treatments. The human mitochondrial protease hClpP potential DIPG therapeutic target, and this study describes the synthesis of two new series tetrahydropyridopyrimidindiones (THPPDs) as activators. Among tested compounds, we have identified 36 (THX6) that shows strong activation (EC50 = 1.18 μM) good cytotoxicity in ONC201-resistant cells (IC50 0.13 μM). Studying oxidation mechanisms on cell membranes, treatment causes change levels fatty acids (PUFAs, MUFAs, SFAs) compared to untreated dysregulates level proteins involved oxidative phosphorylation, biogenesis, mitophagy lead global collapse integrity function suggesting mechanism through which accomplishes its antitumor activity lines.

Язык: Английский

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