Expression of PD-1 and PD-L1 in BCG-treated NMIBC

The recommended treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is intravesical instillations of Bacillus Calmette-Guérin (BCG). Despite completing BCG therapy, up to 40% of patients experience disease recurrence within five years. T cell exhaustion has been associated with poor outcome following treatment with BCG.

In this study, we investigated whether T cell exhaustion, characterized by tumor protein expression of PD-1 and PD-L1 in paired samples obtained before and after BCG treatment could provide further insight into BCG response and help predict outcome in patients with NMIBC.

Tumor samples from 104 patients with NMIBC were collected before and after BCG. Sections from tissue microarrays were stained using immunohistochemistry to analyze the protein expression of PD-1 and PD-L1. Data was analyzed using digital pathology software.

High PD-1 expression was associated with higher tumor stage and grade pre-BCG (p = 0.001 and p = 0.002) and with tumor stage post-BCG (p = 0.005). PD-L1 was associated with higher tumor stage in pre- and post-BCG samples (p = 0.006 and p = 0.048). Patients with low expression of PD-1 and PD-L1 in the pre-BCG tumor had a superior high-grade recurrence-free survival (HG-RFS) compared to patients with high PD-1 (p = 0.008) and PD-L1 (p = 0.006) expression.

Protein expression of the exhaustion markers PD-1 and PD-L1 in pre-BCG tumor samples were correlated to higher stage and grade as well as worse HG-RFS, indicating that T cell exhaustion may play an important role in resistance to BCG treatment.