Immunosuppressive Role of Integrin β8 in Recurrence After Bacillus Calmette-Guérin (BCG) Therapy for Non-Muscle Invasive Bladder Cancer.

Background

Although immunosuppressive factors contribute to the recurrence of non-muscle invasive bladder cancer (NMIBC) during Bacillus Calmette-Guérin (BCG) therapy, the mechanism remains unclear.

Methods

In this study, key players in the immunosuppression associated with recurrence after BCG therapy were identified through comprehensive genetic and functional analyses of untreated NMIBC.

Results

Microarray analysis of bladder cancer tissue from 13 eligible NMIBC patients revealed an association between high expression of integrin β8 (ITGB8) and recurrence after BCG treatment (p < 0.001). In UMUC cells exhibiting high ITGB8 expression, ITGB8 knockdown significantly decreased cell growth, invasion, adhesion, and secretion of the immunosuppressive cytokine transforming growth factor-β1 (TGF-β1, p < 0.01 for each). In addition, ITGB8 and TGF-β1 expression were correlated in immunohistochemistry of surgical specimens from 13 patients (p < 0.05). These results indicate that ITGB8 regulates TGF-β1 secretion.

Conclusions

ITGB8 may contribute to post-BCG therapy recurrence of NMIBC by suppressing tumor immunity through the activation of TGF-β1. Evaluation of ITGB8 expression in preoperative NMIBC could potentially predict recurrence following intravesical BCG therapy.