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Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Emerging immunotherapies for bladder cancer
Joseph W Kim1, Yusuke Tomita, Jane Trepel
1aProstate and Urologic Cancers Program, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut bDevelopmental Therapeutics Branch cGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Purpose Of Review:
Inhibition of immune escape mechanisms, such as the programed death-ligand 1 pathway, has demonstrated rapid, durable responses in multiple tumor types, including advanced urothelial carcinoma. This review discusses emerging immunotherapies for urothelial carcinoma in various stages of clinical development.
Recent Findings:
Urothelial carcinoma has a high mutational burden, which may increase the number of tumor antigens and potentially enhance the ability of the immune system to recognize tumor cells as foreign. However, urothelial carcinoma can evade the immune system by downregulating tumor-antigen presentation, upregulating various immune checkpoints, and inactivating cytotoxic T cells. Immunotherapies for urothelial carcinoma target each of these steps to restore immune-mediated cytotoxicity. Many of these agents are in clinical trials for urothelial carcinoma.
Summary:
Immunotherapies are active in urothelial carcinoma, but only in a fraction of patients, implying the presence of persistent immune escape. Identifying the mechanisms of immune escape and developing rational combinatorial regimens may make the benefit of immunotherapy accessible to a broader population.
Insights
Emerging immunotherapies show promise for advanced urothelial carcinoma by targeting immune escape. Further research into overcoming resistance mechanisms is crucial to expand patient access to these treatments.
Area of Science:
- Oncology
- Immunology
- Urothelial Carcinoma Research
Background:
- Urothelial carcinoma exhibits high mutational burden, potentially increasing tumor antigen recognition.
- However, it employs immune evasion strategies like downregulating antigen presentation and upregulating immune checkpoints.
- These mechanisms inactivate cytotoxic T cells, hindering anti-tumor immunity.
Purpose of the Study:
- To review emerging immunotherapies for urothelial carcinoma.
- To discuss agents in various stages of clinical development.
- To highlight the role of inhibiting immune escape mechanisms, such as the programed death-ligand 1 pathway.
Main Methods:
- Review of clinical trial data for immunotherapies in urothelial carcinoma.
- Analysis of immune escape mechanisms in urothelial carcinoma.
- Discussion of emerging therapeutic strategies targeting these mechanisms.
Main Results:
- Immunotherapies targeting immune escape pathways demonstrate activity in urothelial carcinoma.
- These treatments have shown rapid and durable responses in some patients.
- Many novel immunotherapeutic agents are currently in clinical trials for this cancer type.
Conclusions:
- Immunotherapies are active in urothelial carcinoma but benefit only a subset of patients.
- Persistent immune escape mechanisms limit treatment efficacy.
- Identifying resistance mechanisms and developing combination therapies are key to broadening patient benefit.
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