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

Simple Summary: Patients with non-muscle invasive bladder cancer often receive Bacillus Calmette–Guérin (BCG) therapy to prevent cancer from returning. However, some patients still experience recurrence, and the reasons for this are not fully understood. This study investigated a molecule called integrin β8, which is found on the surface of cancer cells and may weaken the immune response activated by BCG treatment. We analyzed patient tumor samples and bladder cancer cells in the laboratory and found that tumors with high integrin β8 expression also showed increased levels of a substance that suppresses immunity. Patients with higher integrin β8 levels were more likely to have cancer return after BCG therapy. These findings suggest that integrin β8 may help cancer cells escape the immune system and could serve as a useful marker to identify patients at higher risk of recurrence before starting BCG treatment. 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. [ABSTRACT FROM AUTHOR]

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