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Tumor immune dysfunction and exclusion subtypes in bladder cancer and pan-cancer: a novel molecular subtyping
Kun Zheng1, Youlong Hai1, Hongqi Chen2
1Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Journal of Translational Medicine
|April 17, 2024
Summary
A new bladder cancer subtyping method based on tumor immune dysfunction and exclusion (TIDE) effectively predicts immunotherapy response. This approach identifies patient subtypes with distinct prognoses and treatment sensitivities, guiding personalized cancer therapy.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Precise molecular subtyping is crucial for personalized cancer treatment, but current strategies for bladder cancer (BC) are inadequate.
- Tumor immune dysfunction and exclusion (TIDE) significantly impact treatment outcomes and warrant novel subtyping approaches.
Purpose of the Study:
- To develop and validate a novel TIDE-based subtyping strategy for bladder cancer to guide personalized immunotherapy.
- To characterize the heterogeneity and TIDE patterns within BC to identify distinct patient subgroups.
Main Methods:
- Transcriptome data from BC patients was analyzed to evaluate TIDE patterns.
- Consensus clustering using TIDE marker-genes classified BC into subtypes.
- Tumor microenvironment, immunotherapy sensitivity, and clinical validation were assessed using various techniques including RNA-seq, IHC, and ELISA.
Main Results:
- Six TIDE biomarker genes identified, classifying BC into three subtypes with varying TIDE levels, malignancy, and prognosis.
- Subtype I showed high sensitivity to immune checkpoint blockade (ICB), while Subtype III exhibited resistance due to an immunosuppressive microenvironment.
- The TIDE-based subtyping demonstrated superior efficiency in predicting immunotherapy non-responders compared to existing methods and showed conservation across pan-cancers.
Conclusions:
- A novel TIDE-based subtyping method offers a powerful clinical tool for bladder cancer and pan-cancer patients.
- This classification guides personalized therapy by identifying potential beneficiaries and excluding patients resistant to ICB therapy.
- The TIDE subtypes can enhance existing biomarkers and assist in selecting optimal treatment strategies.
