Immunological Risk Stratification of Bladder Cancer Based on Peripheral Blood Natural Killer Cell Biomarkers

Area of Science:

• Immunology
• Oncology
• Genetics

Background:

• Bladder cancer (BC) is highly immunogenic, with Bacillus Calmette-Guérin (BCG) immunotherapy being effective for non-muscle-invasive BC (NMIBC).
• Natural killer cells (NKcs) are crucial for BCG immunotherapy response and cancer immune surveillance.

Purpose of the Study:

• To identify predictive biomarkers for BC by analyzing killer-cell immunoglobulin-like receptors (KIRs), their human leukocyte antigen class-I (HLA-I) ligands, and DNAX Accessory Molecule-1 (DNAM-1/CD226) expression on peripheral blood NKcs.
• To establish an immunological risk stratification for BC patients.

Main Methods:

• KIR/HLA-I genotypes were compared between 132 BC patients, other cancer patients, plasma cell disorder patients, and healthy controls.
• CD226 expression on peripheral blood NKcs was assessed using flow cytometry.
• Statistical analyses included chi-square, ANOVA, Kaplan-Meier, and regression analyses to compare KIR/HLA-I interactions and CD226 expression across groups and survival outcomes.

Main Results:

• Three distinct immunological risk groups (low, intermediate, high) were identified, showing significantly different 10-year progression-free and overall survival rates for both muscle-invasive and NMIBC patients treated with BCG.
• Immunological risk stratification independently predicted survival, outperforming histological staging alone.
• CD226 expression on NKcs enhanced risk stratification accuracy in intermediate-risk BC patients.

Conclusions:

• Immunological risk stratification, based on NK cell receptor profiles, complements histopathology for improved BC patient risk assessment and personalized treatment selection.
• Further understanding of NKc-mediated immune surveillance mechanisms can lead to the development of novel NKc-based therapies for bladder cancer.