The influence of microbiome‐derived amino acids metabolites in shaping the glioma immunosuppressive microenvironment

Deleted Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Abstract Gliomas are the most common intracranial tumors characterized by highly malignant behavior. In addition to genetic and epigenetic mutations, unique cancer microenvironment (CME) plays a pivotal role in glioma progression resistance therapy. Among critical factors CME, amino acid metabolism stands out for its significant influence, with specific acids suppressing anti‐cancer immune responses promoting an immunosuppressive environment. The human microbiota affect host functions, disruptions homeostasis leading metabolic alterations dysfunction various diseases. Emerging evidence highlights of microbiota‐derived metabolites, including acids, reprogramming CME modulating oncogenic signaling pathways. This review examines influence gut microbiome on metabolism—namely, tryptophan, tyrosine, arginine, branched‐chain acids—and evaluates potential roles microbiome‐derived metabolites prognosis diagnosis glioma.

Language: Английский

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Redefining Hepatocellular Carcinoma Treatment: Nanotechnology Meets Tumor Immune Microenvironment

Journal of drug targeting, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 47

Published: March 13, 2025

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide, characterized by its complex pathogenesis and poor therapeutic outcomes. Despite recent advances in targeted molecular therapies, immune checkpoint inhibitors (ICIs), radiotherapy, conventional chemotherapy, five-year survival rate for this neoplasm remains dismally low. The progress nanotechnology has revolutionized cancer treatment years. These provide unprecedented opportunities to overcome current limitations different modalities. This review provides a comprehensive analysis how interfaces with tumor microenvironment (TIME) HCC can present new frontier interventions HCC. We critically overview latest developments nanoparticle-based delivery systems various drugs also other antitumor agents like thermal therapy radiotherapy. highlight unique ability nanoparticles modulate immunosuppressive (TME) enhance efficacy. Furthermore, we analyze emerging strategies that exploit nanoformulations biological barriers drug bioavailability treatment.

Language: Английский

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Multiple roles of branched-chain amino acid metabolism in tumour progression

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: April 9, 2025

Abstract Metabolic reprogramming enables tumour cells to sustain their continuous proliferation and adapt the ever-changing microenvironment. Branched-chain amino acids (BCAAs) metabolites are involved in intracellular protein synthesis catabolism, signal transduction, epigenetic modifications, maintenance of oxidative homeostasis. Alterations BCAA metabolism can influence progression various tumours. However, how is dysregulated differs among depending on type; for example, it manifest as decreased leading accumulation, or enhanced uptake increased catabolism. In this review, we describe role different As well discuss metabolic drives therapy resistance evasion antitumour immune response, these pro-cancer effects achieved part by activating mTORC signalling pathway. In-depth investigations into potential mechanisms which affects tumorigenesis enhance our understanding relationship between cancer provide new strategies therapy.

Language: Английский

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BCAT2 binding to PCBP1 regulates the PI3K/AKT signaling pathway to inhibit autophagy-related apoptosis and ferroptosis in prostate cancer

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 24, 2025

Abstract Prostate cancer (PCa) has emerged as a predominant cause of cancer-related mortality among men globally. The mechanisms branched-chain amino acids (BCAAs) contributing to the development PCa remain inadequately elucidated. objective this study was examine involvement BCAAs and BCAT2 in tumorigenesis. exhibited elevated expression levels tissues cells. Among critical enzymes involved BCAA metabolic pathway, only demonstrated significant closely associated with tumor progression patient prognosis. RNA sequencing along related functional experiments indicated that can inhibit autophagy, autophagy-related apoptosis, ferroptosis PCa. Furthermore, results co-immunoprecipitation, mass spectrometry, other methodologies established PCBP1, downstream protein interacting BCAT2, co-regulates PI3K/AKT thereby influencing Moreover, interacted PCBP1 at Leucine 239 collaboratively regulate signaling which is crucial for initiation Targeting may represent promising therapeutic strategy prevent proliferation

Language: Английский

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Genitourinary cancer neoadjuvant therapies: current and future approaches

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(12), P. 1041 - 1057

Published: Sept. 9, 2023

Neoadjuvant therapies can improve tolerability, reduce tumor volume to facilitate surgery, and assess subsequent treatment response. Therefore, there is much enthusiasm for expanding the benefits of cancer neoadjuvant setting recurrence survival in patients with localized or locally advanced genitourinary (GU) cancer. This approach clinically pertinent because these treatments are administered primarily treatment-naive elicit greatest drug In addition, results not impacted by other anticancer treatments. While have been standard bladder past, they presently restricted clinical trials renal prostate (PCa); however, changes imminent. Precision will be ushered biomarker-stratified appropriate endpoints comprehensive correlative imaging studies. review discusses studies GU malignancies how inform future study design considerations.

Language: Английский

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Bladder cancer intrinsic LRFN2 drives anticancer immunotherapy resistance by attenuating CD8⁺T cell infiltration and functional transition

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(10), P. e007230 - e007230

Published: Oct. 1, 2023

Immune checkpoint inhibitor (ICI) therapy improves the survival of patients with advanced bladder cancer (BLCA); however, its overall effectiveness is limited, and many still develop immunotherapy resistance. The leucine-rich repeat fibronectin type-III domain-containing protein (LRFN) family has previously been implicated in regulating brain dysfunction; mechanisms underlying effect LRFN2 on tumor microenvironment (TME) remain unclear.Here we combined bulk RNA sequencing, single-cell ProcartaPlex multiple immunoassays, functional experiments, TissueFAXS panoramic tissue quantification assays to demonstrate that shapes a non-inflammatory TME BLCA.First, comprehensive multiomics analysis identified as novel immunosuppressive target specific BLCA. We found tumor-intrinsic inhibited recruitment transition CD8+ T cells by reducing secretion pro-inflammatory cytokines chemokines, this mechanism was verified vitro vivo. restrained antitumor immunity inhibiting infiltration, proliferation, differentiation vitro. Furthermore, spatial exclusivity relationship observed between LRFN2+ cell markers programmed death-1 (PD-1) factor 1 (TCF-1). Preclinically, knockdown significantly enhanced efficacy ICI therapy. Clinically, can predict responses real-world public cohorts. Our results reveal new role for immune evasion chemokine T-cell transition.Thus, represents be ICIs provide potential treatment option

Language: Английский

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Identification of FLRT2 as a key prognostic gene through a comprehensive analysis of TMB and IRGPs in BLCA patients

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 29, 2024

Introduction The tumor immune environment and immune-related genes are instrumental in the development, progression, prognosis of bladder cancer (BLCA). This study sought to pinpoint key influencing BLCA decipher their mechanisms action. Methods results We analyzed differentially expressed (DEGs) between high- low- mutational burden (TMB) groups. Subsequently, we constructed a reliable prognostic model based on gene pairs (IRGPs) DEGs low-risk A total 22 shared were identified across differential TMB IRGPs-derived risk groups patients. Through univariate Cox multivariate analyses, highlighted five - FLRT2, NTRK2, CYTL1, ZNF683, PRSS41 significantly correlated with patient prognosis. Notably, FLRT2 emerged as an independent factor for BLCA, impacting via modulation macrophage infiltration microenvironment. Further investigation spotlighted methylation sites cg25120290, cg02305242, cg01832662 regulators expression. Discussion These findings pivotal illuminated intricate dictating not only presents novel marker but also carves out potential avenues immunotherapy targeted therapeutic strategies BLCA. By demystifying profound impact environment, this augments comprehension management cancer.

Language: Английский

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Knowledge-map analysis of bladder cancer immunotherapy

Human Vaccines & Immunotherapeutics, Journal Year: 2023, Volume and Issue: 19(3)

Published: Oct. 30, 2023

This study aimed to conduct a bibliometric analysis in the field of bladder cancer (BC) immunotherapy, and explore research trends, hotspots frontiers from 2000 2022. VOSviewer software was used analyze collaborative relationships between authors, institutions, countries/regions, journals through citation, co-authorship, co-citation analysis, identify this field. Researchers based United States America have published total 627 papers with 27,308 citations. Indeed, USA ranked first among top 10 most active countries showed extensive collaboration other countries. The University Texas MD Anderson CANC CTR has 58 articles, making it institution terms articles research. Kamat AM Lamm DL were co-cited authors 28 980 co-citations, respectively. Chang Yuan Xu le link strength 195. J UROLOGY frequently journal, 100 6,668 co-citations. Studies BC immunotherapy can be broadly classified into three categories: "basic research", "clinical trial", "prognosis". Our findings provide an overview priorities future directions immunotherapy. Tumor microenvironment immune checkpoint inhibitors (ICIs) BC, as well combination ICIs drugs, may become main direction

Language: Английский

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Bcat2‐Mediated Branched‐Chain Amino Acid Catabolism Is Linked to the Aggravated Inflammation in Obese with Psoriasis Mice

Molecular Nutrition & Food Research, Journal Year: 2024, Volume and Issue: 68(8)

Published: April 1, 2024

Abstract Scope: The global prevalence of obesity has significantly increased, presenting a major health challenge. High‐fat diet (HFD)‐induced is closely related to the disease severity psoriasis, but mechanism not fully understood. Methods and results: study utilizes HFD‐induced model along with an imiquimod (IMQ)‐induced psoriasis‐like mouse (HFD‐IMQ) conduct transcriptomics metabolomic analyses. obese mice exhibits more severe lesions compared normal (ND)‐IMQ mice. expression genes IL‐17 signaling pathway ( IL‐17A, IL‐17F, S100A9, CCL20, CXCL1 ) upregulated, leading accumulation T cells neutrophils in skin. Moreover, finds that there inhibition branched‐chain amino acids (BCAAs) catabolism pathway, key gene transferase 2 (Bcat2) downregulated, levels leucine, isoleucine, valine are elevated HFD‐IMQ Furthermore, peroxisome proliferator‐activated receptor gamma (PPAR γ) inhibited, while STAT3 activity promoted Conclusion: amplifies exacerbates potential role played by Bcat2‐mediated BCAAs metabolism. suggests BCAA PPAR γ‐STAT3 exacerbate inflammation psoriasis obesity.

Language: Английский

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Bibliometric insights into drug resistance in bladder cancer: Two decades of progress (1999–2022)

Heliyon, Journal Year: 2024, Volume and Issue: 10(11), P. e31587 - e31587

Published: May 20, 2024

To provide a comprehensive bibliometric overview of drug resistance in bladder cancer (BC) from 1999 to 2022, aiming illuminate its historical progression and guide future investigative avenues. Literature on BC between 2022 was sourced the Web Science. Visual analyses were executed using Vosviewer Citespace software, focusing contributions by countries, institutions, journals, authors, references, keywords. From 2727 publications, marked growth studies discerned over two decades. Prominent among all institutions is University Texas System. The majority top-ranked journals American. In authorship significance, McConkey DJ led while Bellmunt J dominated citations. Research topics predominantly spanned demographics, efficacy evaluations, molecular features, oncology subtypes, individualized treatment strategies, with notable contemporary emphasis mechanisms behind nuances ICIs. Our analysis charts landscape research 2022. While study has been robust, there's an evident need for deeper exploration into intricacies potential ICIs targeted therapeutic strategies.

Language: Английский

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