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Updated: Oct 19, 2025
Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
CD8+ T effector and immune checkpoint signatures predict prognosis and responsiveness to immunotherapy in bladder
Xingyu Chen1, Runshi Xu2, Dong He3
1Department of Oncology, Third Xiangya Hospital, Central South University, 283 Tongzipo Road, Changsha, 410013, China.
Abstract:
Immune-checkpoint blockade (ICB) has been routinely implemented to treat bladder cancer; however, most patients have little or no clinical benefit. In this study, 348 pretreated metastatic urothelial cancer samples from the IMvigor210 cohort were used to identify important genes significantly associated with CD8+ T effector and immune checkpoint signatures. The immune checkpoint inhibitor score (IMS) scoring system was constructed to predict the immunotherapy responsiveness. Transcriptome analysis confirmed that the high IMS score group had significant immune activation with better prognosis and higher immunotherapy responsiveness, which was a powerful biomarker for predicting the prognosis and responsiveness of ICB. Tumor immune dysfunction and exclusion (TIDE) scores were calculated using 2031 external bladder cancer samples for further validation. We selected the important Hub genes as potential therapeutic targets, and validated the genes using genomic, transcriptomic, immunomic, and other multi-omics methods. In addition, we construct a risk prediction model which could stratify patients with bladder cancer and predict patient prognosis and ICB treatment responsiveness. In conclusion, this study identified effective biomarkers for the prediction of immune checkpoint inhibitor treatment responsiveness in bladder cancer patients and provided new immunotherapeutic targets.
Insights
This study introduces an Immune Checkpoint Inhibitor Score (ICIS) to predict bladder cancer immunotherapy response. High ICIS scores indicate better prognosis and treatment success, identifying key biomarkers for immune checkpoint blockade therapy.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Immune-checkpoint blockade (ICB) offers limited benefit for many bladder cancer patients.
- Predictive biomarkers are crucial for optimizing ICB treatment efficacy.
Purpose of the Study:
- To identify genes associated with CD8+ T effector and immune checkpoint signatures in metastatic urothelial cancer.
- To develop and validate a scoring system (Immune Checkpoint Inhibitor Score - ICIS) for predicting ICB response.
- To discover novel therapeutic targets and a risk model for bladder cancer prognosis and immunotherapy.
Main Methods:
- Analysis of 348 metastatic urothelial cancer samples from the IMvigor210 cohort.
- Transcriptome analysis to correlate gene signatures with immune response.
- Calculation of Tumor Immune Dysfunction and Exclusion (TIDE) scores on 2031 external bladder cancer samples.
- Multi-omics validation of selected hub genes and construction of a risk prediction model.
Main Results:
- A high ICIS was significantly associated with enhanced immune activation, improved prognosis, and higher immunotherapy responsiveness.
- The ICIS demonstrated strong potential as a predictive biomarker for ICB treatment in bladder cancer.
- Validated hub genes and a risk model for patient stratification and prognosis prediction.
Conclusions:
- The developed ICIS is an effective biomarker for predicting ICB treatment responsiveness in bladder cancer.
- Identified novel therapeutic targets and a risk prediction model to guide immunotherapy strategies.
- This research enhances personalized treatment approaches for bladder cancer patients undergoing immunotherapy.
