TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells

Nature, Journal Year: 2018, Volume and Issue: 554(7693), P. 544 - 548

Published: Feb. 1, 2018

Language: Английский

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A Consensus Molecular Classification of Muscle-invasive Bladder Cancer

European Urology, Journal Year: 2019, Volume and Issue: 77(4), P. 420 - 433

Published: Sept. 26, 2019

Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, but the diversity of their subtype sets impedes application. To achieve an international consensus on MIBC subtypes that reconciles published classification schemes. We used 1750 transcriptomic profiles from 16 datasets and two additional cohorts. performed network-based analysis six independent systems to identify set classes. Association survival was assessed using multivariable Cox models. report results effort reach subtypes. identified classes: luminal papillary (24%), nonspecified (8%), unstable (15%), stroma-rich basal/squamous (35%), neuroendocrine-like (3%). These classes differ regarding underlying oncogenic mechanisms, infiltration by immune stromal cells, histological characteristics, including provide single-sample classifier assigns class label tumor sample's transcriptome. Limitations work are retrospective data collection lack complete information patient treatment. This system offers robust framework will enable testing validation predictive biomarkers in future prospective trials. Bladder cancers at level, scientists proposed several into While these may be useful stratify patients for prognosis or response treatment, would facilitate use Conducted multidisciplinary expert teams field, this study proposes such provides tool applying setting.

Language: Английский

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Bladder cancer

Nature Reviews Disease Primers, Journal Year: 2017, Volume and Issue: 3(1)

Published: April 12, 2017

Language: Английский

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Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer

Cell, Journal Year: 2018, Volume and Issue: 173(2), P. 515 - 528.e17

Published: April 1, 2018

Language: Английский

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Advances in bladder cancer biology and therapy

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 21(2), P. 104 - 121

Published: Dec. 2, 2020

Language: Английский

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Mechanisms of BCG immunotherapy and its outlook for bladder cancer

Nature Reviews Urology, Journal Year: 2018, Volume and Issue: 15(10), P. 615 - 625

Published: July 10, 2018

Language: Английский

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Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification

The Journal of Pathology, Journal Year: 2017, Volume and Issue: 242(1), P. 113 - 125

Published: Feb. 13, 2017

Abstract Global mRNA expression analysis is efficient for phenotypic profiling of tumours, and has been used to define molecular subtypes almost every major tumour type. A key limitation that most tumours are communities both non‐tumour cells. This problem particularly pertinent advanced invasive which known induce changes responses in the surrounding tissue. To identify bladder cancer tumour‐cell phenotypes compare classification by phenotype with global gene analysis, we analysed 307 cancers (cystectomized) genome immunohistochemistry antibodies 28 proteins. According systematic protein data, focusing on processes, describe five urothelial carcinoma: urothelial‐like, genomically unstable, basal/ SCC ‐like, mesenchymal‐like, small‐cell/neuroendocrine‐like. We provide pathological definitions each subtype. Tumours expressing differentiation factors show inconsistent abnormal terminal markers, suggesting pseudo‐differentiation. Cancers different may co‐cluster (converge), cases identical cluster apart (diverge), analyses. divergence/convergence suggests broad commonalities related process exist between muscle‐invasive regardless specific phenotype. Hence, there a disagreement subtype determined immunohistochemical at level. suggest combination pathology (tumour‐cell phenotype) (context) required adequate cancer. © 2017 The Authors. Journal Pathology published John Wiley & Sons Ltd behalf Pathological Society Great Britain Ireland.

Language: Английский

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An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 16, 2021

Abstract The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed NMIBC ( n = 834). Transcriptomic identifies four classes (1, 2a, 2b and 3) reflecting tumor biology disease aggressiveness. Both transcriptome-based subtyping the level chromosomal instability provide independent prognostic value beyond established clinicopathological parameters. High instability, p53-pathway disruption APOBEC-related mutations are significantly associated transcriptomic class 2a poor outcome. RNA-derived immune cell infiltration chromosomally unstable tumors enriched 2b. Spatial proteomics confirms higher demonstrates association between lower recurrence rates. Finally, documented 1228 validation samples using a single sample classification tool. classifier provides framework for biomarker discovery optimizing treatment surveillance next-generation trials.

Language: Английский

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Genomic Subtypes of Non-invasive Bladder Cancer with Distinct Metabolic Profile and Female Gender Bias in KDM6A Mutation Frequency

Cancer Cell, Journal Year: 2017, Volume and Issue: 32(5), P. 701 - 715.e7

Published: Nov. 1, 2017

Language: Английский

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Molecular Subtypes of Urothelial Bladder Cancer: Results from a Meta-cohort Analysis of 2411 Tumors

European Urology, Journal Year: 2018, Volume and Issue: 75(3), P. 423 - 432

Published: Sept. 10, 2018

Language: Английский

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