Role of immunotherapy in bladder cancer: past, present and future

Butt, Sabeeh-Ur-Rehman; Malik, Laeeq

doi:10.1007/s00280-018-3518-7

Cited by 41 publications

(42 citation statements)

References 83 publications

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“…In melanoma and non-small cell lung cancer, for example, the tumor immune state is recognized for prognostic value and for predictive value in the response to immune checkpoint blockade therapies [ 27 , 28 ]. Immunotherapies are rapidly shifting the treatment priorities for bladder cancer, as well as other human cancers [ 29 ]. Within the last two years, there has been a dramatic shift in the treatment of metastatic iUC with the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Naturally-occurring canine invasive urothelial carcinoma harbors luminal and basal transcriptional subtypes found in human muscle invasive bladder cancer

et al. 2018

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There is growing evidence that molecular subtypes (e.g. luminal and basal subtypes) affect the prognosis and treatment response in patients with muscle invasive urinary bladder cancer (invasive urothelial carcinoma, iUC). Modeling these subtypes in pre-clinical animal studies is essential, but it is challenging to produce these subtypes, along with other critical host and tumor features, in experimentally-induced animal models. This study was conducted to determine if luminal and basal molecular subtypes are present in naturally-occurring canine iUC, a cancer that mimics the human condition in other key aspects. RNA sequencing was performed on 29 canine treatment naive iUC tissue samples and on four normal canine bladder mucosal samples. Data were aligned to CanFam 3.1, and differentially expressed genes were identified. Unsupervised hierarchical clustering of these genes revealed two distinct groups (n = 13, n = 16). When genes that distinguish basal and luminal subtypes in human cancer (n = 2015) were used to probe genes differentially expressed between normal canine bladder and iUC, 829 enriched signature genes were identified. Unsupervised hierarchical clustering of these genes revealed two distinct groups comprised of 18 luminal subtype tumors and 11 basal subtype tumors. The enriched genes included MMP9, SERPINE2, CAV1, KRT14, and RASA3 in basal tumors, and PPARG, LY6E, CTSE, CDK3, and TBX2 in luminal tumors. In supervised clustering, additional genes of importance in human iUC were identified in canine iUC associated with claudin-low and infiltrated tumors. A smaller panel of genes (n = 60) was identified that distinguished canine luminal and basal iUC with overall 93.1% accuracy. Immune signature patterns similar to those in human iUC were also identified with the greatest enrichment of immune genes being in the basal subtype tumors. These findings provide additional compelling evidence that naturally-occurring canine iUC is a highly relevant and much needed model of human iUC for translational research.

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Section: Discussionmentioning

confidence: 99%

Naturally-occurring canine invasive urothelial carcinoma harbors luminal and basal transcriptional subtypes found in human muscle invasive bladder cancer

et al. 2018

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“…BLCA is a frequent malignant disease with rising incidence and high recurrence rates [18]. Although new diagnostic and therapeutic strategies have been carried out over the past several decades, yet the clinical outcome of BLCA patients remains unsatis ed [3,19]. Hence, there is an urging need to develop better diagnostic methods to accurately identify asymptomatic and recurrent individuals in an early stage, and to propose novel treatment targets to improve prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…BLCA is characterized by high rate of recurrence and progression, which impose a considerable economic burden on healthcare system and have substantial effects on the quality of life and overall outcome of BLCA patients. Although novel treatments for BLCA have been proposed, such as immunotherapy of PD-1/PD-L1 [2], the ve-year survival rate for advanced/metastatic BLCA is only 15% and the median overall survival is less than 15 months [3]. Early diagnosis and recurrence monitoring of BLCA would be valuable for better prognosis.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value and underlying mechanism of autophagy-related genes in bladder cancer

Zhang

Wang²,

et al. 2020

Preprint

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Background Bladder cancer (BLCA) is the most common malignancy whose early diagnosis can ensure better prognosis. However, the predictive accuracy of commonly used predictors, including patients’ general condition, histological grade and pathological stage, is insufficient to identify the patients who need invasive treatment. Autophagy is regarded as a vital factor in maintaining mitochondrial function and energy homeostasis in cancer cells. Whether autophagy-related genes (ARGs) can predict the prognosis of BLCA patients deserves to be investigated. Methods Based on BLCA data retrieved from the Cancer Genome Atlas (TCGA) and ARGs list obtained from the Human Autophagy Database (HADb) website, we identified prognosis-related differentially expressed ARGs (PDEARGs) through Wilcox text and constructed a PDEARGs-based prognostic model through multivariate Cox regression analysis. The predictive accuracy, independent forecasting capability, and the correlation between present model and clinical variables or tumor microenvironment (TME) were evaluated through R software. Enrichment analysis of PDEARGs was performed to explore the underlying mechanism, and a systematic prognostic signature with nomogram was constructed by integrating clinical variables and aforementioned PDEARGs-based model. Results We identified several PDEARGs and constructed a PDEARGs-based prognostic model, which could precisely predict the prognosis of BLCA patients. Then, we found that the risk score generated by PDEARGs-based model could effectively reflect deteriorated clinical variables and tumor-promoting microenvironment. Additionally, several immune-related gene ontology (GO) terms were significantly enriched by PDEARGs, which might provide insights for present model and propose potential therapeutic targets for BLCA patients. Finally, a systematic prognostic signature with promoted clinical utility and predictive accuracy was constructed to assist clinician decision. Conclusion PDEARGs are valuable prognostic predictor and potential therapeutic targets for BLCA patients.

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“…Many BC trials are exploring immunotherapy, vaccines, chemotherapy, or gene therapy efficacy for BCG-unresponsive disease, advanced, recurrent, and metastatic BC. For a comprehensive list of drugs for several BC phenotypes, see Butt and Malik (2018), Rouanne et al (2018), and Soria et al (2019), while for specific NMIBCs, BCG-unresponsive, see Tse et al (2019). We included some clinical trials from no.…”

Section: Immunotherapy Of Bladder Cancer: New Frontiersmentioning

confidence: 99%

New Roadmaps for Non-muscle-invasive Bladder Cancer With Unfavorable Prognosis

et al. 2020

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About 70% of bladder cancers (BCs) are diagnosed as non-muscle-invasive BCs (NMIBCs), while the remaining are muscle-invasive BCs (MIBCs). The European Association of Urology (EAU) guidelines stratify NMIBCs into low, intermediate, and high risk for treatment options. Low-risk NMIBCs undergo only the transurethral resection of the bladder (TURB), whereas for intermediate-risk and high-risk NMIBCs, the transurethral resection of the bladder (TURB) with or without Bacillus Calmette-Guérin (BCG) immune or chemotherapy is the standard treatment. A minority of NMIBCs show unfavorable prognosis. High-risk NMIBCs have a high rate of disease recurrence and/or progression to muscle-invasive tumor and BCG treatment failure. The heterogeneous nature of NMIBCs poses challenges for clinical decision-making. In 2020, the EAU made some changes to NMIBCs BCG failure definitions and treatment options, highlighting the need for reliable molecular markers for improving the predictive accuracy of currently available risk tables. Nowadays, next-generation sequencing (NGS) has revolutionized the study of cancer biology, providing diagnostic, prognostic, and therapy response biomarkers in support of precision medicine. Integration of NGS with other cutting-edge technologies might help to decipher also bladder tumor surrounding aspects such as immune system, stromal component, microbiome, and urobiome; altogether, this might impact the clinical outcomes of NMBICs especially in the BCG responsiveness. This review focuses on NMIBCs with unfavorable prognoses, providing molecular prognostic factors from tumor immune and stromal cells, and the perspective of urobiome and microbiome profiling on therapy response. We provide information on the cornerstone of immunotherapy and new promising bladder-preserving treatments and ongoing clinical trials for BCG-unresponsive NMIBCs.

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Role of immunotherapy in bladder cancer: past, present and future

Cited by 41 publications

References 83 publications

Naturally-occurring canine invasive urothelial carcinoma harbors luminal and basal transcriptional subtypes found in human muscle invasive bladder cancer

Naturally-occurring canine invasive urothelial carcinoma harbors luminal and basal transcriptional subtypes found in human muscle invasive bladder cancer

Prognostic value and underlying mechanism of autophagy-related genes in bladder cancer

New Roadmaps for Non-muscle-invasive Bladder Cancer With Unfavorable Prognosis

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