The Dynamic Role of Ferroptosis in Cancer Immunoediting: Implications for Immunotherapy

Pharmacological Research, Journal Year: 2025, Volume and Issue: 214, P. 107674 - 107674

Published: Feb. 27, 2025

Currently, cancer immunotherapy strategies are primarily formulated based on the patient's present condition, representing a "static" treatment approach. However, progression is inherently "dynamic," as immune environment not fixed but undergoes continuous changes. This dynamism characterized by ongoing interactions between tumor cells and cells, which ultimately lead to alterations in microenvironment. process can be effectively elucidated concept of immunoediting, divides development into three phases: "elimination," "equilibrium," "escape." Consequently, adjusting regimens these distinct phases may enhance patient survival improve prognosis. Targeting ferroptosis an emerging area immunotherapy, our findings reveal that antioxidant systems associated with possess dual roles, functioning differently across immunoediting. Therefore, this review delve role system progression. It also propose targeting at different stages, aiming illuminate significant implications various for immunotherapy.

Language: Английский

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Multidimensional transcriptomics based to illuminate the mechanisms of taurine metabolism in immune resistance of pancreatic cancer

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

Published: March 31, 2025

Pancreatic cancer, a highly malignant tumor of the digestive system, is characterized by microenvironment with high degree immunosuppression. This immunosuppressive property poses significant challenges, as it hampers effective infiltration immune cells and impairs their ability to exert cytotoxic effects. The metabolic process taurine has emerged crucial factor in modulating functions activities cells. Intervening metabolism holds potential reshape microenvironment, thereby enhancing recognize eliminate To explore therapeutic relationship between disorders pancreatic cancer immunotherapy, we employed multiple software packages, including "Seurat", "DoubletFinder", "Harmony", "GSVA", "CellChat" analyze single-cell data spatial transcriptomic cancer. In present study, four distinct cell subsets, namely RPS4Y1+ cells, LYZ+ CPE+ MKI67+ were identified for first time. CNV score highlighted role within Through cell-communication analysis, crosstalk among fibroblasts, CD8+ T was identified, offering novel insights into immunotherapy strategies, which strengthened co-localization analysis transcriptomics. Furthermore, conducting combined survival data, LY6D target. co-culture experiments uncovered underlying mechanism regulating imbalance establishment "taurine-immune crosstalk" criteria this study effectively paves way immunotherapy. conclusion, current research underscores significance Targeting may represent approach reversing "stiff-cancer" characteristics

Language: Английский

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Cancer-Associated Fibroblasts as the “Architect” of the Lung Cancer Immune Microenvironment: Multidimensional Roles and Synergistic Regulation with Radiotherapy

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3234 - 3234

Published: March 31, 2025

Cancer-associated fibroblasts (CAFs), as the “architect” of immune microenvironment in lung cancer, play a multidimensional role tumor progression and regulation. In this review, we summarize heterogeneity origin molecular phenotype CAFs explore complex interactions between multiple components microenvironment, including regulatory relationships with innate cells (e.g., tumor-associated macrophages, neutrophils), adaptive T cells), extracellular matrix (ECM). significantly influence immunomodulation through secretion cytokines, remodeling ECM, regulation cell function affects escape treatment resistance tumors. addition, review also deeply explored synergistic relationship CAF radiotherapy, revealing key radiotherapy-induced which provides new perspective for optimizing comprehensive strategy cancer. By comprehensively analyzing roles its interaction aims to provide theoretical basis precise clinical

Language: Английский

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Unveiling purine metabolism dysregulation orchestrated immunosuppression in advanced pancreatic cancer and concentrating on the central role of NT5E

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

Published: April 1, 2025

The dismal efficacy of immunotherapy for Pancreatic cancer (PC) can be predominantly ascribed to its distinctive cold-tumor properties. by-products purine metabolic reprogramming are extensively engaged in tumor immune modulation, influencing the functions and recruitment cells molding an microenvironment that is propitious growth. We harnessed single-cell transcriptomics spatial concurrently analyze metabolism (PM) features PC microenvironment. quantitatively appraised PM traits diverse cell subsets via scoring algorithms such as AUCell Ucell. Moreover, development cell-cell interaction analysis elucidated alterations TME induced by dysregulation. Additionally, we defined disorder characteristics patients utilized this assess phenotypes prognoses patient population. Also, identified crucial intermediate genes impact establishment immunosuppressive environment within PC, validated them through sectioning co-culture experiments. Multi - dimensional transcriptome data unique heterogeneity microenvironment, which manifested fibroblasts demonstrating higher scores TME. Cellchat revealed malignant with elevated expression were concomitantly associated frequent interactions CAFs well high ligand-receptor pairs transcription factors. Spatial further corroborated finding. Furthermore, newly constructed criteria indicated levels a lack response Finally, study singular role NT5E immunosuppression resulting from PC. CCK8 invasion experiments following model demonstrated intervention targeting could reverse augmented malignancy co-cultured CAFs. potentially key target reversing "stiff-cancer" This demonstrates disorders impinge upon exacerbate engendered progression fibrosis. Therapeutic strategies or may offer ray hope advanced PDAC.

Language: Английский

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Metastasis-Directed Therapy in Oligometastatic Prostate Cancer: Biological Rationale and Systematic Review of Published Data

Cancers, Journal Year: 2025, Volume and Issue: 17(8), P. 1256 - 1256

Published: April 8, 2025

Introduction: Metastasis-directed therapy (MDT) alone may be effective in preventing disease progression and positively affecting overall survival (OS) oligometastatic prostate cancer (OMPC). Objective: We systematically reviewed the current literature to analyse biological rationale for integrating MDT into treatment strategies OMPC investigate evidence on its role OMPC. Evidence acquisition: MEDLINE/PUBMED EMBASE Database were searched identify eligible reports published up January 2024. The proceedings of European Society Radiotherapy Oncology, Medical American Radiation Clinical Uro-Oncology Group, Urological Association annual meetings analysed. Results: Eighteen studies between 2014 2024 selected analysis. included 1058 patients treated with metastasis-directed radiotherapy. No statistically significant differences found terms treatment-escalation-free hormone-naïve those hormonal manipulation. By contrast, combination significantly increased both 2 year 4 disease-progression-free (DPFS) rates (p-values < 0.00001 0.006, respectively). In castration-sensitive alone, estimated OS 96.4% (95% confidence interval [CI], 92.9–100%) 89.1% CI, 82.3–96.5%), respectively. group 86.1% CI 79.2–93.7%) 74.8% 64.6.3–86.5%), Conclusions: is associated promising outcomes represents a valuable, valid, often preferable strategy. Combined ADT improves survival, but impact remains uncertain. Given these findings, decision incorporate should tailored individual patient characteristics clinical context. Future research integrate biomarker-based approaches optimise use select best candidates multimodal approach.

Language: Английский

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Reengineering the Tumor Oxygen Microenvironment in Radiotherapy to Enhance T‐Cell Function for Radio‐Immunotherapy

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: April 13, 2025

Abstract Analyzing the relationship between tumor O 2 microenvironment (TOME) and immune during radiotherapy regulating it will provide new insights into combination of immunotherapy. In experiments, is observed that exacerbation hypoxia after activated HIF pathway, which, in turn, led to T‐cell exhaustion by upregulating PD‐L1 expression promoting infiltration MDSCs. To address this, a manganese ion‐doped Au–Pt nanozyme‐coated modulator (Mn‐Nz‐M) designed prepared reengineer TOME. First, high catalase activity Mn‐Nz‐M efficiently generated at tumor‐site, modulating TOME improving efficacy. More importantly, studies vitro vivo showed Mn‐Nz‐M‐mediated improvement can reverse PD‐1 + T cell post activate function. Additionally, Mn 2+ released from simultaneously amplify cGAS‐STING pathway NK cells for anti‐tumor activity. This reengineering strategy radio‐immunotherapy not only eliminates primary solid tumors but also inhibits metastasis, providing potential therapeutic targets enhancing interaction

Language: Английский

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