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 ofintegrin β8(ITGB8) and recurrence after BCG treatment (p< 0.001). In UMUC cells exhibiting high ITGB8 expression,ITGB8knockdown 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 ofITGB8expression in preoperative NMIBC could potentially predict recurrence following intravesical BCG therapy.
背景：尽管免疫抑制因素在卡介苗治疗期间与非肌层浸润性膀胱癌的复发相关，但其具体机制尚不明确。 方法：本研究通过对未经治疗的NMIBC样本进行全面的基因与功能分析，确定了与卡介苗治疗后复发相关的免疫抑制关键因子。 结果：对13例符合条件NMIBC患者的膀胱癌组织微阵列分析显示，整合素β8的高表达与卡介苗治疗后复发显著相关（p<0.001）。在高表达ITGB8的UMUC细胞中，敲低ITGB8可显著抑制细胞增殖、侵袭、粘附及免疫抑制因子转化生长因子-β1的分泌（各项p<0.01）。此外，13例患者手术标本的免疫组化分析显示ITGB8与TGF-β1表达呈正相关（p<0.05），表明ITGB8对TGF-β1分泌具有调控作用。 结论：ITGB8可能通过激活TGF-β1抑制肿瘤免疫，从而促进NMIBC患者卡介苗治疗后的复发。术前评估NMIBC组织中ITGB8的表达水平，或可预测膀胱内卡介苗治疗后的复发风险。
肿瘤(癌症)患者之家