CyTOF analysis identifies unusual immune cells in urine of BCG-treated bladder cancer patients.
CyTOF analysis identifies unusual immune cells in urine of BCG-treated bladder cancer patients.
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DOI：
10.3389/fimmu.2022.970931
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
高度恶性非肌肉浸润性膀胱肿瘤采用经尿道电切术，然后反复膀胱内注入卡介苗(BCG)。虽然大多数膀胱癌患者对卡介苗的治疗反应良好，但没有临床参数预测治疗反应，当治疗失败时，预后非常差。此外，接受卡介苗治疗的NMIBC患者中，有很高比例的患者遭受不良影响，迫使他们停止治疗。因此，及早识别卡介苗治疗失败的患者是非常重要的。在这里，为了确定无反应患者和有放弃治疗风险的患者的早期非侵入性生物标志物，我们纵向分析了膀胱癌患者在卡介苗滴注3-7天后释放到尿液中的细胞的表型。质量细胞分析(CyTOF)显示大量的粒细胞和单核细胞，主要表达活化标志。CD15+CD66b+CD14+CD16+细胞在几个样本中高度丰富；流式细胞仪和定量聚合酶链式反应证实了这些标记物的表达。更强的炎症反应与尿液中细胞数量的增加有关；这不是由于血尿，因为细胞比例与血液中的细胞比例不同。这项先导性研究是对卡介苗治疗过程中尿液细胞的首次细胞学分析，能够识别与治疗反应相关的信息标记物，以便使用常规技术对标记物进行亚选以进行确认。进一步的研究应该在更大的患者队列中联合评估尿液中的细胞和可溶性因子，以确定应答者激活的免疫反应的特征，并确定有可能因卡介苗治疗而出现并发症的患者。
High grade non-muscle-invasive bladder tumours are treated with transurethral resection followed by recurrent intravesical instillations of Bacillus Calmette Guérin (BCG). Although most bladder cancer patients respond well to BCG, there is no clinical parameter predictive of treatment response, and when treatment fails, the prognosis is very poor. Further, a high percentage of NMIBC patients treated with BCG suffer unwanted effects that force them to stop treatment. Thus, early identification of patients in which BCG treatment will fail is really important. Here, to identify early stage non-invasive biomarkers of non-responder patients and patients at risk of abandoning the treatment, we longitudinally analysed the phenotype of cells released into the urine of bladder cancer patients 3-7 days after BCG instillations. Mass cytometry (CyTOF) analyses revealed a large proportion of granulocytes and monocytes, mostly expressing activation markers. A novel population of CD15+CD66b+CD14+CD16+ cells was highly abundant in several samples; expression of these markers was confirmed using flow cytometry and qPCR. A stronger inflammatory response was associated with increased cell numbers in the urine; this was not due to hematuria because the cell proportions were distinct from those in the blood. This pilot study represents the first CyTOF analysis of cells recruited to urine during BCG treatment, allowing identification of informative markers associated with treatment response for sub-selection of markers to confirm using conventional techniques. Further studies should jointly evaluate cells and soluble factors in urine in larger cohorts of patients to characterise the arms of the immune response activated in responders and to identify patients at risk of complications from BCG treatment.
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影响因子：
10.1
作者：
Gabrilovich DI
通讯作者：
Gabrilovich DI
影响因子：
5.2
作者：
Ashiru, Omodele;Esteso, Gloria;Vales-Gomez, Mar
通讯作者：
Vales-Gomez, Mar
影响因子：
7.3
作者：
Maria Garcia-Cuesta, Eva;Lopez-Cobo, Sheila;Vales-Gomez, Mar
通讯作者：
Vales-Gomez, Mar
影响因子：
3.7
作者：
Finck, Rachel;Simonds, Erin F.;Jager, Astraea;Krishnaswamy, Smita;Sachs, Karen;Fantl, Wendy;Pe'er, Dana;Nolan, Garry P.;Bendall, Sean C.
通讯作者：
Bendall, Sean C.
影响因子：
16.6
作者：
Bronte V;Brandau S;Chen SH;Colombo MP;Frey AB;Greten TF;Mandruzzato S;Murray PJ;Ochoa A;Ostrand-Rosenberg S;Rodriguez PC;Sica A;Umansky V;Vonderheide RH;Gabrilovich DI
通讯作者：
Gabrilovich DI