Distinct Infiltration of T Cell Populations in Bladder Cancer Molecular Subtypes.

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Bladder cancer heterogeneity necessitates molecular subtyping for better characterization.
• The immune microenvironment's role in different bladder cancer subtypes remains poorly understood.

Purpose of the Study:

• To analyze the immune compartment, focusing on T cell subpopulations, in relation to bladder cancer molecular subtypes (Lund Taxonomy) and invasiveness.
• To investigate immune cell infiltration and composition differences across molecular subtypes and tumor invasiveness.

Main Methods:

• Flow cytometry and RNA sequencing were employed to analyze immune cells in bladder tumors and normal urothelium.
• T cell subpopulations, including CD8+ T cells and regulatory T cells, were quantified and characterized.
• Results were correlated with tumor invasiveness (non-muscle-invasive vs. muscle-invasive bladder cancer) and molecular subtypes.

Main Results:

• Molecular subtypes, unlike tumor invasiveness alone, showed distinct differences in immune infiltration and composition.
• Basal/Squamous (Ba/Sq) and genomically unstable (GU) subtypes exhibited higher immune infiltration than urothelial-like (Uro) tumors.
• GU tumors had more regulatory T cells, and both GU and Uro tumors showed T cell exhaustion markers (protein level in Uro, transcriptomic in GU).

Conclusions:

• Bladder cancer molecular subtypes significantly influence the tumor immune microenvironment.
• Distinct immune profiles across subtypes suggest the need for tailored immunotherapeutic strategies.
• Targeting specific T cell populations and exhaustion pathways may improve treatment efficacy based on molecular subtype.