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.