Accounting for B-cell Behavior and Sampling Bias Predicts Anti-PD-L1 Response in Bladder Cancer

Area of Science:

• Immunology
• Oncology
• Genomics

Background:

• Cancer immunotherapy primarily focuses on T cells.
• B cells and their products, like immunoglobulins, also play a role in anti-tumor immunity.
• Understanding B cell involvement is crucial for improving cancer treatments.

Purpose of the Study:

• To investigate the role of infiltrating B cells in bladder cancer.
• To identify prognostic indicators for bladder cancer patients.
• To develop a predictive model for anti-PD-L1 therapy response.

Main Methods:

• Analysis of intratumoral immunoglobulin repertoires in bladder cancer patients.
• Dataset analysis of the IMVigor210 anti-PD-L1 immunotherapy cohort.
• Development and validation of the PRIMUS predictor.

Main Results:

• The IgG1/IgA ratio serves as a prognostic indicator for bladder cancer subtypes and anti-PD-L1 response.
• High IgG1/IgA ratios correlate with cytotoxic signatures and T-cell receptor signaling.
• Effector B-cell function, not just antibodies, contributes to anti-tumor responses.
• A combined signature of B cells, NK cells, and T cells most accurately predicts anti-PD-L1 response.
• The PRIMUS predictor outperforms existing methods for identifying responders.

Conclusions:

• The IgG1/IgA ratio is a key prognostic factor in bladder cancer immunotherapy.
• Integrating multiple immune cell signatures enhances prediction of treatment efficacy.
• PRIMUS offers a reliable method for identifying responders in muscle-invasive urothelial carcinoma, including difficult-to-treat tumors.