Bladder cancer research is continuously advancing, from new developments to best standards of care. Explore the links and research highlights below to stay informed and learn more about the latest advancements in the field.
Bladder Cancer Research & Studies
Summaries
The Urinary Microbiota as a Modulator of BCG-Induced Immunotherapy
This study explores the role of the urinary microbiota in modulating immune responses to Bacillus Calmette-Guérin (BCG) immunotherapy in patients with non-muscle invasive bladder cancer (NMIBC). While BCG remains the gold standard treatment for NMIBC, disease recurrence or progression occurs in approximately 30–40% of patients, underscoring the need for a deeper understanding of factors influencing treatment outcomes.The research aims to prospectively analyze the urinary microbiota of patients unresponsive to BCG therapy, investigating the potential association between microbial diversity and therapeutic response. Using mouse models, the study will further examine how disruptions in urinary and gut microbiota influence immune modulation and tumor progression. By unraveling the complex interplay between microbiota composition and immune responses, this research seeks to identify underlying mechanisms that impact treatment efficacy.The ultimate goal of this study is to uncover strategies to improve therapeutic outcomes, reduce recurrence rates, and pave the way for microbiota-informed approaches to enhance patient outcomes in NMIBC management.
Note: This summary was written from the research proposal titled ‘The Urinary Microbiota as a Modulator of BCG-Induced Immunotherapy’, by Dr. Dirk Lange, a research study funded with support from Bladder Cancer Canada.
An integrated immune monitoring approach for sex associated B cell exhaustion in BCG unresponsive NMIBC
This project focuses on improving outcomes for bladder cancer patients, especially those unresponsive to Bacillus Calmette-Guerin (BCG) therapy. Focused on understanding B cell behavior—especially the role of “exhausted” B cells in promoting cancer recurrence—researchers are exploring how specific B cell populations may influence relapse after BCG treatment. Early results reveal that higher densities of certain B cells are linked with rapid recurrence, especially among female patients, who often experience shorter recurrence-free intervals than male patients. This difference may stem from underlying sex-based immune responses, making this study crucial for addressing treatment disparities. Through analysis of patient blood and tissue samples, the team is identifying biomarkers associated with early recurrence, which could guide personalized treatments. Leveraging cutting-edge techniques such as single-cell RNA sequencing, the study will map immune cell changes over time to create an early detection system for high-risk individuals. This pioneering approach not only addresses gender-related differences in bladder cancer outcomes but also establishes a foundation for customized interventions, aiming to improve survival rates and quality of life for all bladder cancer patients.
Note: This summary was written from the research proposal titled ‘An integrated immune monitoring approach for sex associated B cell exhaustion in BCG unresponsive NMIBC’, by Madhuri Koti, D. Robert Siemens (Co-Applicants) David M. Berman, Peter Black, John Sfakianos (collaborators), a research study funded with support from Bladder Cancer Canada.
Role of Natural Killer Cells on the Outcome of Radiation Therapy in Muscle Invasive Bladder Cancer
This on-going study focuses on enhancing treatment outcomes for patients with muscle-invasive bladder cancer (MIBC) by investigating the combined effects of radiation therapy and natural killer (NK) cell therapy. NK cell therapy is a type of immunotherapy that uses special immune cells called natural killer cells to fight cancer. These cells are part of the body’s natural defense system and can recognize and destroy abnormal cells, including cancer cells. In this study, researchers will extract NK cells, activate them in the laboratory to enhance their cancer-fighting abilities, and then infuse them back into the body along with radiation treatment. The research seeks to determine if adding NK cell therapy to standard radiation can enhance its effectiveness, especially for patients who do not respond well to current treatments. By using a mouse model and human tumor samples, the study will assess how this combination affects tumor growth and patient responses. The goal is to develop a more effective treatment approach that preserves the bladder while improving survival rates and quality of life for MIBC patients. The findings from this study will potentially pave the way for personalized treatment options that leverage the immune system’s capabilities against cancer.
Note: This summary was written from the research proposal titled ‘Investigate the Role of Natural Killer Cells on the Outcome of Radiation Therapy in Muscle Invasive Bladder Cancer,’ by Dr. W. Kassouf, a research study funded with support from Bladder Cancer Canada.
The Role of OSR1 in Bladder Cancer
Recent studies indicate that the Odd-skipped related 1 (Osr1) transcription factor may function as a tumor suppressor gene across various cancers, including lung, gastric, and renal cell carcinoma. While exploring the role of Osr1 in bladder cancer, researchers observed reduced Osr1 gene expression in tumor specimens from bladder cancer patients compared to adjacent control tissue. Building on this, their study further aims to investigate how Osr1, identified as a potential tumor suppressor, influences the development and progression of muscle-invasive bladder cancer. The research will utilize genetically modified mouse models alongside a carcinogen challenge to examine the effects of Osr1 loss in the bladder’s uroepithelium and stromal compartments. Additionally, the team will employ advanced molecular techniques to identify Osr1 DNA targets in urothelial cancer cells. This multi-faceted approach seeks to elucidate the mechanisms by which Osr1 may suppress tumor growth and invasion, with a particular focus on its impact on epithelial-to-mesenchymal transition and collagen deposition in the tumor microenvironment. The findings from this study could potentially reveal new biomarkers for bladder cancer prognosis and identify novel therapeutic targets, ultimately contributing to improved treatments for this aggressive form of cancer.
Note: This summary was written from the research proposal titled ‘The role of Osr1 in bladder cancer’, by Alonso CAI, Kassouf W, Gupta IR, et al., a research study funded with support from Bladder Cancer Canada.
Immune reprogramming and response to BCG therapy in patients with bladder cancer
Bacillus Calmette-Guérin (BCG) immunotherapy has been the gold standard for treating high-risk non-muscle invasive bladder cancer (NMIBC) patients for over 50 years. However, patients’ response to BCG varies, making it challenging to predict individual outcomes. Recent research suggests that trained immunity (TI) in peripheral blood monocytes, induced by BCG, could serve as a biomarker for predicting treatment response and recurrence-free survival.
TI is a long-lasting memory in innate immune cells, triggered by inflammatory stimuli like BCG. It involves metabolic and epigenetic reprogramming of cells such as monocytes, macrophages, and dendritic cells. Studies have shown that higher levels of TI, indicated by increased IL-12 secretion, are associated with patients without recurrence. Additionally, distinct epigenetic changes, specifically histone modifications, were observed in monocytes from patients with different recurrence outcomes, which could be leveraged to predict responses to BCG therapy. To further investigate the trends in transcriptomic and epigenetic profiles of peripheral blood mononuclear cells from NMIBC patients after BCG therapy, researchers plan to use single-cell RNA sequencing (scRNAseq) and ATAC-seq platform to elucidate the link between immune reprogramming and treatment response. Overall, trained immunity induced by BCG may offer a promising biomarker for predicting treatment outcomes in NMIBC patients.
Note: This summary was written from the research proposal titled ‘Immune reprogramming and response to BCG therapy in patients with bladder cancer’, by Dr. C. Graham, a research study funded with support from Bladder Cancer Canada.
The role of the urinary microbiome in determining response to intravesical BCG in high-risk non-muscle-invasive bladder cancer
The BCG vaccine is the most effective intravesical therapy for non-muscle invasive bladder cancer and is commonly used after surgery to prevent tumour recurrences. When injected into the bladder, BCG acts as an immunostimulatory agent, triggering an anti-tumour immune system response that recognizes and stops tumour cells from proliferating. Recent studies have shown that the immune system’s response to disease is influenced by the bacterial populations that naturally live in our bodies. In a study proposed by researchers at the University of British Columbia and the Cleveland Clinic, investigators will examine the type of immune system responses induced by BCG in bladder cancer, and whether these responses are mediated by imbalances in bladder and gut bacterial populations. This research will further our understanding of why BCG treatment efficacy varies between patients with non-muscle invasive bladder cancer and provides a way forward for improving therapeutic outcomes via the regulatory role of bacteria.
Authors: Othman D, Jalanko T, Reike M, Moskalev I, Nelson B, Hussein A, Tin C, Roumigué M, Ferreira D, Contreras-Sanz A, Maas M, Miller A, Black PC, & Lange D
Published: March 2023