Comprehensive Landscape of Non-muscle Invasive Bladder Cancer Tumour Microenvironment and Prognostic value of Cancer-Associated Myofibroblasts DOI Creative Commons
Carmen Gómez del Cañizo, Félix Guerrero-Ramos,

Mercedes Perez Escavy

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 27, 2023

ABSTRACT BACKGROUND Non-muscle-invasive bladder cancer (NMIBC) poses clinical challenges due to its high recurrence and progression rates. While Bacillus Calmette-Guérin (BCG) remains as the gold standard treatment for high-risk NMIBC, recent irruption of anti-PD-1/PD-L1 drugs claims a comprehensive understanding tumour microenvironment (TME) these tumors. METHODS The present prospective study consisted on analysis 98 fresh NMIBC samples, tumor non-pathological tissue, via flow cytometry. Final included distribution 11 cell types expression PD-L1 in 66 62 tissue biopsies from 73 patients (84.4% paired samples). results were validated using publicly available transcriptomic data, histology. RESULTS In comparison TME presented microvascular alterations, increased cancer-associated fibroblast (CAF) myofibroblast (myoCAF) presence, varied immune distribution. Heterogeneous was observed across subsets, with cells primary potential anti-PD-L1 binding targets. Unbiased revealed that myoCAF M2-like macrophages are enriched grade tumors, but only associated higher rates recurrence, we confirmed three independent cohorts (888 total patients). We further prognostic value myoCAFs by micro-array. CONCLUSION This provides roadmap establish full landscape NMIBĆs TME, highlighting markers. FUNDING funded FC AECC (INVES222946GARC), Consejería de Educación, Ciencia y Universidades la CAM (2018-T2/BMD-10342), Hoffmann-La Roche, Ministerio e Innovación (INMUNOEPIBLA) ISCIII/FEDER (CIBERONC CB16/12/00489)

Language: Английский

Urinary extracellular vesicles-encapsulated miRNA signatures: A new paradigm for urinary bladder cancer diagnosis and classification DOI
Sukhad Kural, Garima Jain, Sakshi Agarwal

et al.

Urologic Oncology Seminars and Original Investigations, Journal Year: 2024, Volume and Issue: 42(7), P. 179 - 190

Published: April 8, 2024

Language: Английский

Citations

8
The role of tumor metabolism in modulating T-Cell activity and in optimizing immunotherapy DOI Creative Commons
Shonik Ganjoo, Priti Gupta,

Halil Ibrahim Corbali

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 26, 2023

Immunotherapy has revolutionized cancer treatment and revitalized efforts to harness the power of immune system combat a variety types more effectively. However, low clinical response rates differences in outcomes due variations landscape among patients with continue be major limitations immunotherapy. Recent improve responses immunotherapy have focused on targeting cellular metabolism, as metabolic characteristics cells can directly influence activity metabolism cells, particularly T cells. Although pathways various been extensively reviewed, intersections these pathways, their potential use targets for improving immune-checkpoint blockade therapies, are not completely understood. This review focuses interplay between tumor metabolites T-cell dysfunction well relationship several patterns activity/function immunology. Understanding relationships could offer new avenues basis.

Language: Английский

Citations

12
Key immune cells and their crosstalk in the tumor microenvironment of bladder cancer: insights for innovative therapies DOI Creative Commons

Antimo Di Spirito,

Sahar Balkhi, Veronica Vivona

et al.

Exploration of Targeted Anti-tumor Therapy, Journal Year: 2025, Volume and Issue: 6

Published: March 31, 2025

Bladder cancer (BC) is a heterogeneous disease associated with high mortality if not diagnosed early. BC classified into non-muscle-invasive (NMIBC) and muscle-invasive (MIBC), MIBC linked to poor systemic therapy response recurrence rates. Current treatments include transurethral resection Bacillus Calmette-Guérin (BCG) for NMIBC radical cystectomy chemotherapy and/or immunotherapy MIBC. The tumor microenvironment (TME) plays critical role in progression, metastasis, therapeutic efficacy. A comprehensive understanding of the TME’s complex interactions holds substantial translational significance developing innovative treatments. TME can contribute resistance, particularly immune checkpoint inhibitor (ICI) therapies, where resistance arises from tumor-intrinsic changes or extrinsic factors. Recent advancements highlight importance research address these challenges. Strategies overcome focus on remodeling transform immunologically “cold” tumors, which lack cell infiltration, “hot” tumors that respond better immunotherapy. These strategies involve disrupting cancer-microenvironment interactions, inhibiting angiogenesis, modulating components enhance anti-tumor responses. Key mechanisms cytokine involvement [e.g., interleukin-6 (IL-6)], phenotypic alterations macrophages natural killer (NK) cells, plasticity cancer-associated fibroblasts (CAFs). Identifying potential targets within improve outcomes patients. This review emphasizes complexity its impact guiding novel approaches, offering hope survival

Language: Английский

Citations

0
Infiltrating Natural Killer cells influence the efficacy of BCG immunotherapy in non-muscle-invasive bladder cancer DOI Creative Commons
Mariana Zuliani Theodoro de Lima, Diogo Assed Bastos, Romulo Loss Mattedi

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 270, P. 155997 - 155997

Published: May 6, 2025

Language: Английский

Citations

0
Bladder cancer immune-related markers: diagnosis, surveillance, and prognosis DOI Creative Commons
Tiantian Yang,

Wanru Luo,

Jie Yu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 4, 2024

As an immune-related tumor type, bladder cancer has been attracting much attention in the study of its markers. In recent years, researchers have made rapid progress markers for cancer. Studies shown that play important role diagnosis, prognosis assessment and treatment addition, detection can also be used to evaluate efficacy immunotherapy predict response patients. Therefore, depth expression their application clinic is great significance expected provide new breakthroughs individualized Future studies will focus more on how detect with low cost high accuracy, as well develop immunotherapeutic strategies bring better therapeutic outcomes

Language: Английский

Citations

2
The role of E3 ubiquitin ligases and deubiquitinases in bladder cancer development and immunotherapy DOI Creative Commons
Xuemei Wang, Ying Zhang, Yao Wu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 5, 2023

Bladder cancer is one of the common malignant urothelial tumors. Post-translational modification (PTMs), including ubiquitination, acetylation, methylation, and phosphorylation, have been revealed to participate in bladder initiation progression. Ubiquitination PTM, which conducted by E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme E3 ubiquitin-protein ligase. ubiquitin ligases play a key role oncogenesis progression drug resistance cancer. Therefore, this review, we summarize current knowledge regarding functions development. Moreover, provide evidence regulation immunotherapy Furthermore, mention multiple compounds that target improve therapy efficacy We hope our review can stimulate researchers clinicians investigate whether how targeting acts novel strategy for therapy.

Language: Английский

Citations

6
Bladder Cancer, Loss of Y Chromosome, and New Opportunities for Immunotherapy DOI
Arun K. Mankan,

N. Mankan,

Begoña de las Heras

et al.

Advances in Therapy, Journal Year: 2024, Volume and Issue: 41(3), P. 885 - 890

Published: Jan. 10, 2024

Language: Английский

Citations

1
Intravesical Gemcitabine and Docetaxel Therapy for BCG-Naïve Patients: a Promising Approach in Non-Muscle Invasive Bladder Cancer DOI Open Access
Mirko Bakula, Tvrtko Hudolin, Nikola Knežević

et al.

Published: April 30, 2024

Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report outcomes of sequential intravesical adminis-tration gemcitabine docetaxel (Gem/Doce) as the first-line treatment BCG-naïve high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, enrolled 52 followed protocol set University Iowa. Follow-up assessments were con-ducted every 3 months. cohort, 25 (48.1%) diagnosed T1HG cancer, 10 (19.2%) had carcinoma situ (CIS), 17 (32.7%) combination CIS+T1HG. Median time to first recurrence T1HG, CIS T1HG+CIS groups was 11, 10.5 8.8 months, respectively. The recurrence-free survival 98.1%, 94.2% 80.8% at 6, 9 12 rate progression-free 100%, 98.1% 92.3% We demonstrated safety Gem/Doce HR during one-year follow-up. Further research extended follow-up, well direct comparison other anticancer agents, are essential.

Language: Английский

Citations

1
Epigenetic changes associated with Bacillus Calmette-Guerin (BCG) treatment in bladder cancer DOI Creative Commons

L Picard,

Fenella J. Rich,

Diane Kenwright

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(5), P. 189123 - 189123

Published: May 26, 2024

Bacillus Calmette-Guérin (BCG) treatment for non-muscle invasive bladder cancer (NMIBC) is an established immunotherapeutic, however, a significant portion of patients do not respond to treatment. Despite extensive research into the therapeutic mechanism BCG, gaps remain in our understanding. This review specifically focuses on epigenomic contributions immune microenvironment, context BCG NMIBC. We also summarise current understanding NMIBC epigenetic characteristics, and discuss how future targeted strategies therapy should incorporate both biomarkers conjunction with genomic biomarkers.

Language: Английский

Citations

1
Development of a propionate metabolism-related gene-based molecular subtypes and scoring system for predicting prognosis in bladder cancer DOI Creative Commons
Fu‐Chun Zheng,

Zhipeng Wang,

Sheng Li

et al.

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: July 29, 2024

Bladder cancer (BLCA) is a prevalent malignancy. Dysregulated propionate metabolism, key factor, suggests potential target for treating metastatic cancer. However, complete understanding of the link between metabolism-related genes (PMRGs) and bladder lacking. From Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases, we gathered BLCA patient data, which was classified into distinct subgroups using non-negative matrix factorization (NMF). Survival pathway analyses were conducted these clusters. The PMRGs model, created through univariate Cox least absolute shrinkage selection operator (LASSO) analyses, assessed prognostic significance Kaplan-Meier receiver operating characteristic (ROC) curves. A comprehensive evaluation included clinical, tumor microenvironment (TME), drug sensitivity, immunotherapy analyses. Finally, expression HSD17B1 essential confirmed via quantitative real-time polymerase chain reaction (qRT-PCR), with further validation Transwell, wound healing, colony-formation, EDU assays. We discovered two subcategories (CA CB) within NMF analysis, CA demonstrating significantly better overall survival compared to CB. Additionally, six emerged as critical factors associated metabolism prognosis. analysis revealed that high-risk correlated poorer prognosis in patients. Moreover, significant differences observed groups terms infiltrated immune cells, checkpoint expression, TME scores, sensitivity. Notably, found suppressing gene inhibited invasion cells. Our study proposes molecular subtypes PMRG-based score promising indicators BLCA. cellular experiments underscore pivotal role metastasis invasion, suggesting its novel therapeutic target.

Language: Английский

Citations

1