Role of tertiary lymphoid structures and B cells in clinical immunotherapy of gastric cancer

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 7, 2025

Gastric cancer is a common malignant tumor of the digestive tract, and its treatment remains significant challenge. In recent years, role various immune cells in microenvironment progression has gained increasing attention. Immunotherapy, primarily based on checkpoint inhibitors, notably improved prognosis patients with gastric cancer; however, challenges regarding therapeutic efficacy persist. Histological features within microenvironment, such as tertiary lymphoid structures (TLSs), tumor-infiltrating lymphocytes, proportion intratumoral stroma, are emerging potentially effective prognostic factors. cancer, TLSs may serve local hubs, enhancing ability to interact recognize antigens, which closely linked effectiveness immunotherapy survival rates patients. However, specific cell type driving TLS formation tumors not yet been elucidated. Mature B-cell regions containing germinal centers. During center formation, B undergo transformations become mature function, exerting anti-tumor effects. Therefore, targeting could provide new avenues for immunotherapy. This review, combined current research elaborates relationship between aiming guidance precise

Язык: Английский

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The role of cisplatin in modulating the tumor immune microenvironment and its combination therapy strategies: a new approach to enhance anti-tumor efficacy

Annals of Medicine, Год журнала: 2025, Номер 57(1)

Опубликована: Янв. 6, 2025

Cisplatin is a platinum-based drug that frequently used to treat multiple tumors. The anti-tumor effect of cisplatin closely related the tumor immune microenvironment (TIME), which includes several cell types, such as tumor-associated macrophages (TAMs), cytotoxic T-lymphocytes (CTLs), dendritic cells (DCs), myeloid-derived suppressor (MDSCs), regulatory T (Tregs), and natural killer (NK) cells. interaction between these can promote survival chemoresistance, decrease efficacy monotherapy. Therefore, various combination treatment strategies have been devised enhance patient responsiveness therapy. augment responses in with checkpoint blockers (such PD-1/PD-L1 or CTLA4 inhibitors), lipid metabolism disruptors (like FASN inhibitors SCD inhibitors) nanoparticles (NPs), resulting better outcomes. Exploring TIME will help identify potential therapeutic targets for improving outcomes cancer patients.

Язык: Английский

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Integrated multi-omics analysis reveals key genetic, metabolic, and microbial drivers in bladder cancer insights into molecular subtyping and therapeutic approaches: A tumor marker prognostic study

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Background: Bladder cancer (BLCA) is a common malignancy with significant impact on patient health. The aim of this study was to explore the potential mechanisms BLCA through combination multi-omics and single-cell analyses. Methods: In study, samples from paracancerous tissues were collected for transcriptome, whole-exome sequencing, metabolome intratumoural microbiome sequencing. These data then co-analyzed publicly available datasets identify analyze key genes, metabolites microbiomes as well their regulatory in pathogenesis BLCA. Different clusters identified basis genes. Differences among investigated terms biological pathways, immunological microenvironment, genetic alterations, immunotherapy drug susceptibility. prognostic value genes analyzed using data, molecular further investigated. Finally, expression patterns observed at single cell level cells identified. Results: In paper, three (AHNAK, CSPG4, NCAM1), 90 two microorganisms (Sphingomonas koreensis Rhodospirillaceae) analysis. Of these, negatively correlated. transcriptome sequencing divided into cluster 1 2 based Single-cell analysis nine types, fibroblasts exhibiting highest thus establishing study. Notably, AHNAK higher fibroblast subtypes. Conclusion: The combined revealed correlation between NCAM1) multiple microorganisms, which offering new reference theoretical support treatment research

Язык: Английский

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Disulfidptosis related immune genes drive prognostic model development and tumor microenvironment characterization in bladder urothelial carcinoma

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 8, 2025

The intricate nature and varied forms of bladder urothelial carcinoma (BLCA) highlight the need for new indicators to define tumor prognosis. Disulfidptosis, a novel form cell death, is closely linked BLCA progression, prognosis, treatment outcomes. Our current goal develop disulfidptosis-related immune prognostic model enhance strategies. Utilizing RNA-seq data from Cancer Genome Atlas (TCGA) , which included 419 patients (19 normal, 400 tumor), we performed weighted gene co-expression network analysis (WGCNA) identify disulfidptosis-associated genes. Through multivariate Cox regression, least absolute shrinkage selection operator (LASSO) regularization, established risk scoring system. A nomogram combining score clinical features predicted Model performance was validated through survival curve independent validation cohort. Immune checkpoints, infiltration, mutation load were assessed. Differential enrichment conducted. Prognostic genes via in vitro experiments. Eight related disulfidptosis identified verified outperformed previous ones predicting overall (OS) high- low-risk groups. Patients with scores had higher OS rates burden (TMB) compared high-risk patients. CD4 memory T cells, CD8 M1 macrophages, resting NK cells found be group. checkpoint inhibitor (ICI) may more effective High-risk group exhibited stronger correlation cancer malignant pathways. Knocking out necrosis factor receptor superfamily member 12 (TNFRSF12A) inhibits proliferation invasion while overexpressing it has opposite effect. We constructed that combines genes, demonstrating good prediction performance. discovered TNFRSF12A an oncogene BLCA, help provide personalized guidance individualized immunotherapy certain extent.

Язык: Английский

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Circular RNAs: driving forces behind chemoresistance and immune evasion in bladder cancer

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

Язык: Английский

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From Bench to Bladder: The Rise in Immune Checkpoint Inhibition in the Treatment of Non-Muscle Invasive Bladder Cancer

Cancers, Год журнала: 2025, Номер 17(7), С. 1135 - 1135

Опубликована: Март 28, 2025

Non-muscle invasive bladder cancer (NMIBC) represents a significant clinical challenge due to its high recurrence rate and need for frequent monitoring. The current treatment modality is bacillus Calmette-Guérin (BCG) therapy combined with chemotherapy after transurethral resection of the tumor (TURBT), which highly effective in most patients. Yet, becomes resistant these treatments 30-40% patients, necessitating new modalities. In world, development immune checkpoint inhibitors that target molecules, such as programmed cell death protein-1 (PD-1), ligand, PD-L1, Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), have revolutionized many types. PD-1/PD-L1 CTLA-4 are shown be upregulated NMIBC certain circumstances. interactions play role evasion by suppressing T activity within microenvironment (TME), while binding on cells leads downregulation response, making pathways potential immunotherapeutic targets NMIBC. This review seeks understand therapies treating We explore cellular non-cellular landscape TME NMIBC, including Tregs, effector cells, macrophages, B relevant cytokines. also discuss biological covering rationale immunotherapies Finally, we cover key trials studied clinically. Such study will helpful urologists oncologists manage patients more effectively.

Язык: Английский

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A Novel Approach for Bladder Cancer Treatment: Nanoparticles as a Drug Delivery System

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 13461 - 13483

Опубликована: Дек. 1, 2024

Bladder cancer represents one of the most prevalent malignant neoplasms urinary tract. In Asian context, it eighth common in males. 2022, there were approximately 613,791 individuals diagnosed with bladder worldwide. Despite availability efficacious treatments for two principal forms cancer, namely non-invasive and invasive high incidence recurrence following treatment suboptimal outcomes observed patients high-grade advanced disease represent significant concerns management at this juncture. Nanoparticles have gained attention their excellent properties, including stable physical a porous structure that can be loaded variety substances, so on. The in-depth research on nanoparticles has led to emergence as new class combination therapy, due advantageous properties. These include extension drug release window, enhancement bioavailability, improvement targeting ability, reduction local systemic toxicity, simultaneous delivery multiple drugs therapy. As result, become novel agent system. advent provided impetus development non-surgical chemotherapy, immunotherapy, gene therapy phototherapy. unique properties facilitated diverse therapeutic modalities, enhancing overall efficacy. This review examines recent advancements use treatments, encompassing aspects such delivery, efficacy, associated toxicity nanoparticles, well challenges encountered clinical applications.

Язык: Английский

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Advances in preclinical assessment of therapeutic targets for bladder cancer precision medicine

Current Opinion in Urology, Год журнала: 2024, Номер 34(4), С. 251 - 257

Опубликована: Апрель 10, 2024

Purpose of review Bladder cancer incidence is on the rise, and until recently, there has been little to no change in treatment regimens over last 40 years. Hence, it imperative work strategies approaches untangle complexity intra- inter-tumour heterogeneity bladder with aim improving patient-specific care outcomes. The focus this therefore highlight novel targets, advances, therapy for patients. Recent findings success combining an antibody-drug conjugate (ADC) immunotherapy recently hailed as a game changer treating interest other ADCs option also rife. Furthermore, overcome chemoresistance standard have described recently. In addition, studies showed that targeting genomic alterations (e.g. mutations FGFR3 , DNA damage repair genes loss Y chromosome) could be helpful prognostic stratification biomarkers. use single-cell RNA sequencing allowed better characterisation tumour microenvironment subsequent identification targets. Functional precision medicine another avenue improve guide personalized options. Summary Several preclinical targets options validation these advances will lead development implementation robust

Язык: Английский

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The Ketone Bridge Between the Heart and the Bladder: How Fast Should We Go?

International Neurourology Journal, Год журнала: 2024, Номер 28(Suppl 1), С. 2 - 11

Опубликована: Фев. 27, 2024

Metabolic syndrome (MS) is associated with both cardiovascular and bladder dysfunction. Insulin resistance (IR) central obesity, in particular, are the main risk factors. In these patients, vicious pathological cycles exacerbate abnormal carbohydrate metabolism sustain an inflammatory state, serious implications for heart bladder. Ketone bodies serve as alternative energy source this context. They considered a "super-fuel" because they generate adenosine triphosphate less oxygen consumption per molecule, thus enhancing metabolic efficiency. have positive impact on all components of MS. aid weight loss glycemic control, lower blood pressure, improve lipid profiles, enhance endothelial function. Additionally, possess direct anti-inflammatory, antioxidant, vasodilatory properties. A shared key player dysfunction formation NLRP3 inflammasome, which ketone inhibit. Interventions that elevate body levels-such fasting, ketogenic diet, supplements, sodium-glucose cotransporter 2 inhibitors-have been shown to directly affect outcomes urinary tract symptoms derived from This review explores pathophysiological basis benefits cardiac

Язык: Английский

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Integrative analysis of the bladder cancer from a cell cycle NCAM1 perspective at both single cell and bulk resolution

Environmental Toxicology, Год журнала: 2024, Номер unknown

Опубликована: Апрель 6, 2024

Abstract Introduction Bladder cancer (BLCA) is a prevalent and deadly form of urinary cancer, there need for effective therapies, particularly muscle‐invasive bladder (MIBC). Cell cycle inhibitors show promise in restoring control the cell BLCA cells, but their clinical prognosis evaluation limited. Methods Transcriptome scRNA‐seq data were collected from Cancer Genome Atlas Program (TCGA)‐BLCA GSE190888 cohort, respectively. R software Seurat package used analysis, including quality control, dimensionality reduction, identification differentially expressed genes. Genes related to obtained genecards website, protein–protein interaction network analysis was performed using cytoscape software. Functional enrichment immune infiltration drug sensitivity molecular docking conducted various tools packages. lines cultured transfected vitro experimental assays, RT‐qPCR CCK‐8 viability assays. Results We identified 32 genes as independent risk or protective factors prediction. revealed involvement regulation, apoptosis, signaling pathways. Using these genes, we developed nomogram predicting survival, which displayed high stratification efficacy patients. Four associated key identified, NCAM1, HBB, CKD6, CTLA4. also main types patients investigated functional differences between epithelial cells based on expression levels Furthermore, observed positive correlative relationship cancer‐associated fibroblasts score value. Finally, experiments demonstrate suppressive role NCAM1 proliferation. Conclusion These findings suggest that could serve potential biomarkers may represent therapeutic targets development more therapies. Hopefully, provide valuable insights into mechanisms perspective cycle. Moreover, novel proliferation suppressor carcinogenesis.

Язык: Английский

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