Nathan J Mackenzie, Kate Zimmermann, Clarissa Nicholls, Mahasha Pj Perera, Alexander Ngoo, Penny L Jeffery, Ian Vela, Tony J Kenna, Elizabeth D Williams, Patrick B Thomas
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引用次数: 0
Abstract
Treatments targeting the immune system only benefit a subset of patients with bladder cancer (BC). Biomarkers predictive of BC progression and response to specific therapeutic interventions are required. We evaluated whether peripheral blood immune subsets and expression of clinically relevant immune checkpoint markers are associated with clinicopathologic features of BC. Peripheral blood mononuclear cells isolated from blood collected from 23 patients with BC and 9 age-matched unaffected-by-cancer control donors were assessed using a 21-parameter flow cytometry panel composed of markers of T, B, natural killer and myeloid populations and immune checkpoint markers. Patients with BC had significantly lower numbers of circulating CD19+ B cells and elevated circulating CD4+CD8+ T cells compared with the control cohort. Immune checkpoint markers programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) were elevated in the total peripheral immune cell population in patients with BC. Within the BC cohort, PD-1 expression in T and myeloid cells was elevated in muscle-invasive compared with non-muscle-invasive disease. In addition, elevated T, B and myeloid PD-1 cell surface expression was significantly associated with tumor stage, suggesting that measures of peripheral immune cell exhaustion may be a predictor of tumor progression in BC. Finally, positive correlations between expression levels of the various immune checkpoints both overall and within key peripheral blood immune subsets collected from patients with BC were observed, highlighting likely coregulation of peripheral immune checkpoint expression. The peripheral blood immunophenotype in patients with BC is altered compared with cancer-free individuals. Understanding this dysregulated immune profile will contribute to the identification of diagnostic and prognostic indicators to guide effective immune-targeted, personalized treatments.
针对免疫系统的治疗只能使一部分膀胱癌(BC)患者受益。需要能预测膀胱癌进展和对特定治疗干预反应的生物标志物。我们评估了外周血免疫亚群和临床相关免疫检查点标记物的表达是否与膀胱癌的临床病理特征相关。从 23 名 BC 患者和 9 名年龄匹配的未受癌症影响的对照供血者的血液中分离出外周血单核细胞,使用 21 个参数的流式细胞仪面板进行评估,该面板由 T、B、自然杀伤细胞、髓样细胞群标记物和免疫检查点标记物组成。与对照组相比,BC 患者的循环 CD19+ B 细胞数量明显减少,而循环 CD4+CD8+ T 细胞数量增加。免疫检查点标记物程序性细胞死亡蛋白1(PD-1)和T细胞免疫球蛋白和含粘蛋白域-3(TIM-3)在BC患者的外周免疫细胞总数中升高。在 BC 患者群中,肌肉浸润性疾病的 T 细胞和骨髓细胞中 PD-1 的表达高于非肌肉浸润性疾病。此外,T、B和髓系PD-1细胞表面表达的升高与肿瘤分期显著相关,这表明外周免疫细胞衰竭的测量值可能是预测BC肿瘤进展的一个指标。最后,从 BC 患者采集的外周血免疫亚群中观察到,各种免疫检查点的表达水平在整体上和关键亚群中都呈正相关,这表明外周血免疫检查点的表达可能存在核心关联。与未患癌症的人相比,BC 患者的外周血免疫表型发生了改变。了解这种失调的免疫特征将有助于确定诊断和预后指标,从而指导有效的免疫靶向个性化治疗。
期刊介绍:
The Australasian Society for Immunology Incorporated (ASI) was created by the amalgamation in 1991 of the Australian Society for Immunology, formed in 1970, and the New Zealand Society for Immunology, formed in 1975. The aim of the Society is to encourage and support the discipline of immunology in the Australasian region. It is a broadly based Society, embracing clinical and experimental, cellular and molecular immunology in humans and animals. The Society provides a network for the exchange of information and for collaboration within Australia, New Zealand and overseas. ASI members have been prominent in advancing biological and medical research worldwide. We seek to encourage the study of immunology in Australia and New Zealand and are active in introducing young scientists to the discipline.