Identification and validation of an excellent prognosis subtype of muscle-invasive bladder cancer patients with intratumoral CXCR5+CD8+T cell abundance
Identification and validation of an excellent prognosis subtype of muscle-invasive bladder cancer patients with intratumoral CXCR5+CD8+T cell abundance
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肿瘤内 CXCR5( )CD8( )T 细胞丰度的肌层浸润性膀胱癌患者良好预后亚型的鉴定和验证
DOI：
10.1080/2162402x.2020.1810489
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发表时间：
2020-01-01
期刊：
影响因子：
7.2
通讯作者：
Zhang, Weijuan
中科院分区：
文献类型：
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作者：
Huang, Qiuren;Zhou, Quan;Zhang, Weijuan
膀胱癌是世界上第九种最常见的疾病，具有很高的发病率和死亡率。研究表明，在各种肿瘤类型中，CXCR5(+)CD8(+)T细胞与较好的预后相关，但其在肌肉浸润性膀胱癌(MIBC)中的作用尚不清楚。本研究对来自3个队列(中山医院141例、上海肿瘤中心108例、肿瘤基因组图谱403例)的662例MIBC患者进行了回顾性分析。对11例MIBC新鲜切除标本进行CXCR5(+)、CD8(+)T细胞表型分析，并对402例TCGA MIBC患者进行生物信息学分析。研究发现，肿瘤内CXCR5(+)CD8(+)T细胞的丰度预示着较高的总体生存率和无病生存率。肿瘤组织中CXCR5(+)CD8(+)T细胞浸润率高的患者从辅助化疗(ACT)中获益更多。瘤内CXCR5(+)CD8(+)T细胞具有细胞溶解和自我更新的特点。值得注意的是，CXCR5(+)CD8(+)T细胞主要存在于MIBC的基底层和基质丰富的亚型中，而CXCR5(+)CD8(+)T细胞丰富的肿瘤表现出有限的FGFR3信号和激活的免疫治疗和EGFR相关途径。综上所述，我们发现肿瘤内CXCR5(+)CD8(+)T细胞丰度的MIBC预后良好，对ACT敏感。CXCR5(+)CD8(+)T细胞密度高的肿瘤对免疫治疗和EGFR靶向治疗具有潜在的敏感性。CXCR5(+)CD8(+)T细胞为MIBC提供了一种新的潜在生物标志物和治疗靶点。
Bladder cancer is the ninth most frequent-diagnosed disease worldwide, bearing high morbidity and mortality rates. Studies have shown that a particular population of CXCR5(+)CD8(+)T cells was associated with superior prognosis in various tumor types, and yet its role in muscle-invasive bladder cancer (MIBC) remains unclear. In this study, 662 MIBC patients from 3 cohorts (Zhongshan Hospital,n= 141; Shanghai Cancer Center,n= 108; The Cancer Genome Atlas,n= 403) were analyzed retrospectively. 11 fresh resected samples of MIBC were examined to characterize the phenotype of CXCR5(+)CD8(+)T cells and 402 MIBC patients from TCGA were applied for bioinformatics analysis. It was explored that the abundance of intratumoral CXCR5(+)CD8(+)T cells indicated superior overall survival and disease-free survival. Patients with a higher infiltration of CXCR5(+)CD8(+)T cells in tumor tissue benefit more from adjuvant chemotherapy (ACT). Intratumoral CXCR5(+)CD8(+)T cells displayed cytolytic and self-renewal features. Remarkably, CXCR5(+)CD8(+)T cells were mainly presented in the basal and stromal-rich subtypes of MIBC and tumors with enriched CXCR5(+)CD8(+)T cells showed limited FGFR3 signaling signature and activated immunotherapeutic and EGFR associated pathway. In conclusion, we identified an excellent prognosis and ACT sensitive subtype of MIBC with intratumoral CXCR5(+)CD8(+)T cell abundance. Tumors with high density of CXCR5(+)CD8(+)T cells possessed potential sensitivity to immunotherapy and EGFR-targeted therapy. CXCR5(+)CD8(+)T cells provide a new potential biomarker as well as a therapeutic target in MIBC.