Immune phenotype of peripheral blood mononuclear cells in patients with high-risk non-muscle invasive bladder cancer.

Immune phenotype of peripheral blood mononuclear cells in patients with high-risk non-muscle invasive bladder cancer.
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DOI:
10.1007/s00345-018-2359-7
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发表时间:
2018-11
影响因子:
3.4
通讯作者:
Sfakianos JP
Sfakianos JP
中科院分区:
医学2区
文献类型:
--
作者:
Audenet F;Farkas AM;Anastos H;Galsky MD;Bhardwaj N;Sfakianos JP

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目的探讨高危非肌性浸润性膀胱癌(NMIBC)患者外周血单个核细胞(PBMC)的免疫表型。我们前瞻性地收集了在我院接受治疗的高危NMIBC患者的血液样本。流式细胞术检测PBMC中T细胞和NK细胞的频率以及免疫调节分子(Tim-3、TIGIT、PD-1)的表达。纳入健康供者的PBMC进行比较,并调查其与卡介苗应答的关系。共纳入38例患者,其中19例bcg应答,19例bcg难治性。NMIBC患者NK细胞总频率显著高于HD患者(15.2% [IQR: 11.4, 22.2] vs. 5.72% [IQR: 4.84, 9.79]; p=0.05), T细胞总频率无统计学差异。Tim-3和TIGIT在NMIBC中的表达均显著高于HD,特别是在NK细胞中(分别为13.8%[11.0;22.4]比5.56%[4.20;10.2]和34.9%[18.9;53.5]比1.82% [0.63;5.16],p <0.001)。总的来说,在NMIBC患者和HD患者中,PD-1在所有细胞类型中的表达都很低。接种卡介苗前后免疫表型无显著差异。然而,应答者在卡介苗前CD8+ T细胞的比例明显更高。高风险NMIBC患者的PBMC免疫表型与HD患者存在显著差异,无论是否存在疾病或是否开始BCG。外周CD8+ T细胞可能在BCG应答中发挥作用。
To explore the immune phenotype of peripheral blood mononuclear cells (PBMC) in patients with high-risk non-muscle invasive bladder cancer (NMIBC). We prospectively collected blood samples from patients with high-risk NMIBC treated at our institution. PBMC were analyzed by flow cytometry to determine the frequency of T cells and NK cells and expression of immunoregulatory molecules (Tim-3, TIGIT, and PD-1). PBMC from healthy donors (HD) were included for comparison and associations with response to BCG were investigated. A total of 38 patients were included, 19 BCG-responders and 19 BCG-refractory. Compared to 16 PBMC from HD, the frequency of total NK cells was significantly higher in patients with NMIBC (15.2% [IQR: 11.4, 22.2] vs. 5.72% [IQR: 4.84, 9.79]; p=0.05), whereas the frequency of T cells, was not statistically different. Both Tim-3 and TIGIT expression were significantly higher in NMIBC compared to HD, particularly in NK cells (13.8% [11.0; 22.4] vs. 5.56% [4.20; 10.2] and 34.9% [18.9; 53.5] vs. 1.82% [0.63; 5.16], respectively; p <0.001). Overall, the expression of PD-1 in all cell types was low in both NMIBC patients and HD. The immune-phenotype was not significantly different before and after initiation of BCG. However, the proportion of CD8+ T cells before BCG was significantly higher in responders. The immune phenotype of PBMC from patients with high-risk NMIBC was significantly different from HD, regardless of the presence of disease or the initiation of BCG. Peripheral CD8+ T cells could play a role in response to BCG.
DOI: 10.1038/nrc3239
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