Therapeutic rationale of targeting BCG and immune checkpoints in non–muscle-invasive bladder cancer: Is this the Future?

2019 ◽  
Vol 37 (6) ◽  
pp. 343-345
Author(s):  
Andrea K. Lindner ◽  
Tobias Klatte ◽  
Eva Comperat ◽  
Isabel Heidegger ◽  
Renate Pichler
2020 ◽  
Vol 3 (6) ◽  
pp. 789-801
Author(s):  
Malte W. Vetterlein ◽  
J. Alfred Witjes ◽  
Yohann Loriot ◽  
Gianluca Giannarini ◽  
Maarten Albersen ◽  
...  

2018 ◽  
Vol 36 (9) ◽  
pp. 413-422 ◽  
Author(s):  
Tom J.N. Hermans ◽  
Charlotte S. Voskuilen ◽  
Michiel S. van der Heijden, ◽  
Bernd J. Schmitz-Dräger ◽  
Wassim Kassouf ◽  
...  

Chirurgia ◽  
2020 ◽  
Vol 115 (1) ◽  
pp. 89
Author(s):  
Bogdan Florin Geavlete ◽  
Cosmin Victor Ene ◽  
Georgiana Xenia Bălan ◽  
Cătălin Andrei Bulai ◽  
Dragoş Adrian Georgescu ◽  
...  

Author(s):  
Xiaonan Zheng ◽  
Xinyang Liao ◽  
Ling Nie ◽  
Tianhai Lin ◽  
Hang Xu ◽  
...  

Background: Studies have demonstrated the significance of multiple biomarkers for bladder cancer. Here, we attempt to present biomarkers potentially predictive of the prognosis and immunotherapy response of muscle-invasive bladder cancer (MIBC).Method: Immune and stromal scores were calculated for MIBC patients from The Cancer Genome Atlas (TCGA). Core differential expression genes (DEGs) with prognostic value were identified and validated using an independent dataset GSE31684. The clinical implications of prognostic genes and the inter-gene correlation were presented. The distribution of tumor-infiltrating immune cells (TICs), the correlation with tumor mutation burden (TMB), and the expression of eight immune checkpoint–relevant genes and CD39 were accordingly compared. Two bladder cancer cohorts (GSE176307 and IMvigor210) receiving immunotherapy were recruited to validate the prognostic value of LCK and CD3E for immunotherapy.Results: 361 MIBC samples from TCGA revealed a worse overall survival for higher stromal infiltration (p = 0.009) but a better overall survival for higher immune infiltration (p = 0.042). CD3E and LCK were independently validated by TCGA and GSE31684 to be prognostic for MIBC. CD3E was the most correlative gene of LCK, with a coefficient of r = 0.86 (p < 0.001). CD8+ T cells and macrophage M1 are more abundant in favor of a higher expression of CD3E and LCK in MIBC and across pan-cancers. Immune checkpoints like CTLA4, CD274 (PD-1), and PDCD1 (PD-L1) were highly expressed in high-CD3E and high-LCK groups for MIBC and also for pan-cancers, except for thymoma. LCK and CD3E had a moderate positive correlation with CD39 expression. Importantly, high-LCK and high-CD3E groups had a higher percentage of responders than the low-expression groups both in GSE176307 (LCK: 22.73vs. 13.64%, CD3E: 22.00 vs. 13.16%) and IMvigor210 cohorts (LCK: 28.19 vs. 17.45%, CD3E: 25.50 vs. 20.13%).Conclusion: CD3E and LCK were potential biomarkers of MIBC. CD3E and LCK were positively correlated with several regular immunotherapy biomarkers, which is supported by real-world outcomes from two immunotherapy cohorts.


2017 ◽  
Vol 51 (2) ◽  
pp. 87-94 ◽  
Author(s):  
Per-Uno Malmström ◽  
Sachin Agrawal ◽  
Mats Bläckberg ◽  
Peter J. Boström ◽  
Bernard Malavaud ◽  
...  

2021 ◽  
Vol 17 ◽  
pp. 117693432110492
Author(s):  
Xianglai Xu ◽  
Yelin Wang ◽  
Sihong Zhang ◽  
Yanjun Zhu ◽  
Jiajun Wang

We aimed to discover prognostic factors of muscle-invasive bladder cancer (MIBC) and investigate their relationship with immune therapies. Online data of MIBC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO) database. Weighted gene co-expression network analysis (WGCNA) and univariate Cox analysis were applied to classify genes into different groups. Venn diagram was used to find the intersection of genes, and prognostic efficacy was proved by Kaplan-Meier analysis. Heatmap was utilized for differential analysis. Riskscore (RS) was calculated according to multivariate Cox analysis and evaluated by receiver operating characteristic curve (ROC). MIBC samples from TCGA and GEO were analyzed by WGCNA and univariate Cox analysis and intersected at 4 genes, CLK4, DEDD2, ENO1, and SYTL1. Higher SYTL1 and DEDD2 expressions were significantly correlated with high tumor grades. Riskscore based on genes showed great prognostic efficiency in predicting overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in TCGA dataset ( P < .001). The area under the ROC curve (AUC) of RS reached 0.671 in predicting 1-year survival and 0.653 in 3-year survival. KEGG pathways enrichment filtered 5 enriched pathways. xCell analysis showed increased T cell CD4+ Th2 cell, macrophage, macrophage M1, and macrophage M2 infiltration in high RS samples ( P < .001). In immune checkpoints analysis, PD-L1 expression was significantly higher in patients with high RS. We have, therefore, constructed RS as a convincing prognostic index for MIBC patients and found potential targeted pathways.


Sign in / Sign up

Export Citation Format

Share Document