Immune landscape of muscle-invasive bladder cancer: role of TIGIT, LAG-3, and PD-L1

Introduction: Muscle-invasive bladder cancer (MIBC) is an aggressive disease that typically requires multimodal treatment. Recently, immunotherapy strategies targeting the tumor microenvironment (TME) have reshaped the therapeutic approach for MIBC. Our study explores the expression of immune checkpoint biomarkers TIGIT, LAG-3, and PD-L1 across molecular subtypes of MIBC. Methods: Immunohistochemical analysis was performed on archival tumor samples from 62 patients, evenly split between luminal and basal molecular MIBC subtypes. Results: The findings revealed that luminal MIBC patients with high stromal LAG-3 expression had significantly worse survival outcomes compared to those with the basal subtype, establishing LAG-3 as an independent prognostic marker of poor survival in luminal MIBC. In the basal subtype, LAG-3 was more frequently expressed in the stroma than in the luminal subtype. TIGIT expression was consistently detected in both stromal cells and epithelial tumor cells, highlighting its potential as an immunotherapy target. PD-L1 expression showed a positive correlation with both LAG-3 and TIGIT levels in the stroma across both subtypes. The strong immune activity of these ligands underscores their potential as targets for immunotherapy. Discussion: These results may enhance the understanding of MIBC's immune landscape and help identify patient subgroups who could benefit from immune-based treatments. However, validation in larger patient cohorts is needed to confirm the clinical relevance of these biomarkers.