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Updated: Jun 15, 2026
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Genomic Profiling and Immune Phenotyping of Neuroendocrine Bladder Cancer
Jingyu Zang1, Akezhouli Shahatiaili1, Mei-Chun Cai1
1State Key Laboratory of Systems Medicine for Cancer, Department of Radiation Oncology, Department of Urology, Ren Ji Hospital, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Purpose:
Neuroendocrine bladder cancer (NEBC) poses a formidable clinical challenge and attracts keen interests to explore immunotherapy as a viable treatment option. However, a comprehensive immunogenomic landscape has yet to be thoroughly investigated.
Experimental Design:
Leveraging a long-term cohort of natural NEBC cases, we employed a multimodal approach integrating genomic (n = 19), transcriptomic (n = 3), single-cell RNA sequencing (n = 1), and IHC analyses (n = 34) to meticulously characterize the immunogenicity and immunotypes of primary NEBC tumors. Information on clinical, pathologic, medical imaging, and treatment aspects was retrospectively retrieved and analyzed.
Results:
Our study unveiled that despite a considerable mutational burden, NEBC was typically immunologically inactive, as manifested by the "immune-excluded" or "immune-desert" microenvironment. Interestingly, a subset of mixed NEBC with concurrent urothelial bladder cancer histology displayed an "immune-infiltrated" phenotype with prognostic relevance. When compared with urothelial bladder cancer, NEBC lesions were distinguished by a denser cellular composition and augmented peritumoral extracellular matrix, which might collectively impede lymphatic infiltration. As a result, single-agent immune checkpoint inhibitors demonstrated limited efficacy against NEBC, whereas pharmacologic immunostimulation with combination chemotherapy conferred a more favorable response.
Conclusions:
These new insights derived from genomic profiling and immune phenotyping pave the way for rational immunotherapeutic interventions in patients with NEBC, with the potential to ultimately reduce mortality from this otherwise fatal disease.
