Department of Urology, Istanbul University- Cerrahpasa, Cerrahpasa School of Medicine, Istanbul, Turkey.
Department of Biochemistry, Istanbul University- Cerrahpasa, Cerrahpasa School of Medicine, Istanbul, Turkey.
Int J Clin Pract. 2021 May;75(5):e13959. doi: 10.1111/ijcp.13959. Epub 2021 Jan 5.
Mast cells play a critical role in cancer-associated immunity. We aimed to determine the predictive value of urinary mast cell mediators in patients with non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) immunotherapy.
In this prospective study, 19 patients who received immunotherapy because of NMIBC (Group 1) and 19 healthy participants (Group 2) were enrolled. Urine samples were collected to assay N-methylhistamine, histamine, and tryptase levels immediately before the first BCG instillation, immediately after the third and sixth instillations, and 4 weeks after the sixth instillation in Group 1 and at a single visit in Group 2. The changes in urinary markers because of BCC response, BCG instillation, and the presence of NMIBC were assessed.
The average age was 56.1 ± 10.5 years in Group 1 and 52.6 ± 9.7 years in Group 2. Fourteen patients had high-grade Ta tumours and five had T1 tumours. While 12 patients had responded to the BCG, seven patients did not respond to the BCG. There was no correlation between mast cell mediators and BCG response. The N-methylhistamine and histamine levels significantly increased with the onset of immunotherapy, and N-methylhistamine levels significantly decreased when immunotherapy was terminated (P < .05). The pre-BCG estimated marginal mean values of N-methylhistamine were significantly higher in Group 1 than in Group 2 (P < .05).
Our study is the first to identify the changes in mast cell mediators with the onset of immunotherapy and in presence of bladder cancer. However, these mediators cannot predict patients' response to immunotherapy.
肥大细胞在癌症相关免疫中发挥着关键作用。我们旨在确定尿肥大细胞介质在接受卡介苗(BCG)免疫治疗的非肌肉浸润性膀胱癌(NMIBC)患者中的预测价值。
在这项前瞻性研究中,19 名因 NMIBC 而接受免疫治疗的患者(第 1 组)和 19 名健康参与者(第 2 组)入组。第 1 组患者在接受第 1 次 BCG 灌注前、第 3 次和第 6 次灌注后立即以及第 6 次灌注后 4 周采集尿液样本,以测定 N-甲基组氨酸、组胺和类胰蛋白酶水平;第 2 组仅在单个时间点采集尿液样本。评估 BCC 反应、BCG 灌注和 NMIBC 存在引起的尿标志物变化。
第 1 组的平均年龄为 56.1±10.5 岁,第 2 组为 52.6±9.7 岁。14 名患者患有高级 Ta 肿瘤,5 名患者患有 T1 肿瘤。12 名患者对 BCG 有反应,7 名患者对 BCG 无反应。肥大细胞介质与 BCG 反应之间无相关性。随着免疫治疗的开始,N-甲基组氨酸和组胺水平显著升高,当免疫治疗结束时,N-甲基组氨酸水平显著降低(P<.05)。第 1 组患者在接受 BCG 治疗前的估计边际均值 N-甲基组氨酸水平明显高于第 2 组(P<.05)。
本研究首次确定了免疫治疗开始时和膀胱癌存在时肥大细胞介质的变化,但这些介质不能预测患者对免疫治疗的反应。