Deciphering the influence of urinary microbiota on FoxP3+regulatory T cell infiltration and prognosis in Chinese patients with non-muscle-invasive bladder cancer
Deciphering the influence of urinary microbiota on FoxP3+regulatory T cell infiltration and prognosis in Chinese patients with non-muscle-invasive bladder cancer
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解读尿液微生物群对中国非肌层浸润性膀胱癌患者 FoxP3 调节性 T 细胞浸润和预后的影响
DOI：
10.1007/s13577-021-00659-0
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发表时间：
2022-01-15
期刊：
影响因子：
4.3
通讯作者：
Wu, Peng
中科院分区：
文献类型：
--
作者：
Qiu, Yifeng;Gao, Yubo;Wu, Peng
尽管越来越多的证据表明尿微生物群失调与膀胱癌密切相关，但尿微生物群对膀胱癌免疫逃避和肿瘤生长的影响尚不清楚。本研究探讨尿微生物群是否影响非肌肉浸润性膀胱癌肿瘤内FoxP3+调节性T细胞浸润、Ki-67表达及临床预后。40例男性患者，分别有12例和28例复发或无复发。术前采集中游尿样。采用16s rDNA测序分析尿液菌群组成。测定了α和β多样性。LEfSe分析用于鉴定与复发相关的特定细菌。免疫组化法检测肿瘤内FoxP3+调节性T细胞浸润及Ki-67表达。复发患者α-多样性高于无复发患者（Shannon指数，P= 0.0007； Simpson指数，P= 0.0004）。在复发组和非复发组之间观察到明显的β多样性（加权UnifracP= 0.02；非加权UnifracP= 0.001）。LEfSe分析显示，复发组明显富集假单胞菌、葡萄球菌、棒状杆菌和不动杆菌属。尽管微生物多样性与FoxP3+调节性T细胞浸润无关（P= 0.1653），但α多样性高的患者Ki-67表达高于α多样性低的患者（P= 0.0194）。尿微生物多样性较低的患者与多样性较高的患者相比，无复发生存期延长。尿微生物群的紊乱可能导致免疫逃避和肿瘤生长，最终导致不良后果。需要进一步的研究来证实尿微生物群在调节膀胱癌的抗肿瘤免疫反应和生存中的因果作用。
Despite increasing evidence that dysbiosis of urinary microbiota is closely correlated with bladder cancer, the influence of the urinary microbiota on immune evasion and tumor growth in bladder cancer is unknown. This study investigated whether the urinary microbiota influences intratumoral infiltration of FoxP3+ regulatory T cells, expression of Ki-67 and clinical prognosis in non-muscle-invasive bladder cancer. Forty male patients, including 12 and 28 with or without recurrence, respectively, were retrospectively enrolled. Midstream urine samples were preoperatively collected. Urinary microbiota composition was analyzed by 16s rDNA sequencing. Alpha and beta diversities were measured. LEfSe analysis was employed to identify specific bacteria associated with recurrence. Intratumoral infiltration of FoxP3+ regulatory T cells and Ki-67 expression were evaluated by immunohistochemistry. Patients with recurrence had higher α-diversity compared to those without (Shannon Index,P= 0.0007, Simpson Index,P= 0.0004). Distinct beta diversity was observed between recurrence and non-recurrence groups (weighted UnifracP= 0.02; unweighted UnifracP= 0.001). LEfSe analysis showed that the recurrence group displayed marked enrichment ofPseudomonas,Staphylococcus, Corynebacterium, andAcinetobactergenera. Patients with higher alpha diversity had elevated Ki-67 expression than those with lower alpha diversity (P= 0.0194), although microbial diversity was unassociated with infiltration of FoxP3+ regulatory T cells (P= 0.1653). Patients with lower urinary microbial diversity had prolonged recurrence-free survival compared to those with higher diversity. Perturbation of urinary microbiota may induce immune evasion and tumor growth, eventually contributing to unfavorable outcomes. Additional study is warranted to confirm a causal role of urinary microbiota in modulating antitumor immune response and survival in bladder cancer.