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根治性膀胱切除术治疗的肌层浸润性膀胱癌患者中,年龄和性别对免疫细胞浸润标志物和免疫检查点通路的表达水平无影响。

Age and sex have no impact on expression levels of markers of immune cell infiltration and immune checkpoint pathways in patients with muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy.

机构信息

Department of Surgery, Division of Urology, Southern Illinois University School of Medicine, Springfield, IL, USA.

VCORE-Center for Outcomes Research, Analytics, and Evaluation, Vattikuti Urology Institute, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, MI, 48202, USA.

出版信息

Cancer Immunol Immunother. 2019 Jun;68(6):991-997. doi: 10.1007/s00262-019-02340-w. Epub 2019 Apr 17.

Abstract

OBJECTIVES

Advanced age and female sex have been associated with worse outcomes in patients undergoing radical cystectomy for muscle-invasive bladder cancer. A reduced immune response has been implicated as a mechanism. The objective of our study was to analyze the expression patterns of various cellular proteins active in bladder cancer immune pathways, and assess the correlation between age, sex, and the expression of these immune markers.

METHODS

We obtained surgical tissue samples from equally distributed male/female patients with/without lymph node metastasis who had undergone radical cystectomy for urothelial carcinoma (UC) of the bladder (n = 50). Immunohistochemistry (IHC) for CD3 (cluster of differentiation), CD4, CD8, CD56, LAG-3 (lymphocyte-activation gene), TIM-3 (T-cell immunoglobulin and mucin-domain), PD-1 (programmed death) and PD-L1 molecules was performed and scored by a single pathologist (high versus low). Spearman's correlation and Chi square tests investigated the association between age, sex, and IHC results.

RESULTS

Mean age at surgery was 67 years (range 50-78 years); all patients were Caucasians. The following percent of patients scored high for a stain: 18% CD3, 10% CD4, 0% CD8, 0% CD56, 20% LAG-3, 4% TIM-3, 0% PD-1 and 0% PD-L1. There was no association between patients' age, sex, and the expression of any of the immune markers (p > 0.05 for all).

CONCLUSIONS

The association between advanced age, female sex, and worse outcomes in bladder cancer may be independent of the immune pathways active in the disease that we examined in this study.

摘要

目的

在接受根治性膀胱切除术治疗肌层浸润性膀胱癌的患者中,高龄和女性与较差的预后相关。免疫反应减弱被认为是一种机制。本研究的目的是分析在膀胱癌免疫途径中活跃的各种细胞蛋白的表达模式,并评估年龄、性别与这些免疫标志物表达之间的相关性。

方法

我们从接受根治性膀胱切除术的男性/女性、有/无淋巴结转移的膀胱癌患者中获得了等量的手术组织样本(n=50)。对 CD3(分化簇)、CD4、CD8、CD56、LAG-3(淋巴细胞激活基因)、TIM-3(T 细胞免疫球蛋白和粘蛋白结构域)、PD-1(程序性死亡)和 PD-L1 分子进行免疫组织化学(IHC)染色,并由一名病理学家进行评分(高与低)。采用 Spearman 相关检验和卡方检验分析年龄、性别与 IHC 结果之间的关系。

结果

手术时的平均年龄为 67 岁(范围 50-78 岁);所有患者均为白种人。高染色的患者百分比如下:18% CD3、10% CD4、0% CD8、0% CD56、20% LAG-3、4% TIM-3、0% PD-1 和 0% PD-L1。患者的年龄、性别与任何免疫标志物的表达之间均无相关性(所有 p 值>0.05)。

结论

在膀胱癌中,高龄、女性与较差的预后之间的关联可能与我们在本研究中检测到的疾病中活跃的免疫途径无关。

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