Huang Qiuren, Zhou Quan, Zhang Hongyu, Liu Zhaopei, Zeng Han, Chen Yifan, Qu Yang, Xiong Ying, Wang Jiajun, Chang Yuan, Xia Yu, Wang Yiwei, Liu Li, Zhu Yu, Xu Le, Dai Bo, Guo Jianming, Wang Zewei, Bai Qi, Zhang Weijuan
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Oncoimmunology. 2020 Aug 28;9(1):1810489. doi: 10.1080/2162402X.2020.1810489.
Bladder cancer is the ninth most frequent-diagnosed disease worldwide, bearing high morbidity and mortality rates. Studies have shown that a particular population of CXCR5CD8 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, = 141; Shanghai Cancer Center, = 108; The Cancer Genome Atlas, = 403) were analyzed retrospectively. 11 fresh resected samples of MIBC were examined to characterize the phenotype of CXCR5CD8 T cells and 402 MIBC patients from TCGA were applied for bioinformatics analysis. It was explored that the abundance of intratumoral CXCR5CD8 T cells indicated superior overall survival and disease-free survival. Patients with a higher infiltration of CXCR5CD8 T cells in tumor tissue benefit more from adjuvant chemotherapy (ACT). Intratumoral CXCR5CD8 T cells displayed cytolytic and self-renewal features. Remarkably, CXCR5CD8 T cells were mainly presented in the basal and stromal-rich subtypes of MIBC and tumors with enriched CXCR5CD8 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 CXCR5CD8 T cell abundance. Tumors with high density of CXCR5CD8 T cells possessed potential sensitivity to immunotherapy and EGFR-targeted therapy. CXCR5CD8 T cells provide a new potential biomarker as well as a therapeutic target in MIBC.
膀胱癌是全球第九大最常被诊断出的疾病，发病率和死亡率都很高。研究表明，特定群体的CXCR5⁺CD8⁺ T细胞与多种肿瘤类型的较好预后相关，但其在肌层浸润性膀胱癌（MIBC）中的作用仍不清楚。在本研究中，对来自3个队列（中山医院，n = 141；上海癌症中心，n = 108；癌症基因组图谱，n = 403）的662例MIBC患者进行了回顾性分析。检查了11份新鲜切除的MIBC样本以表征CXCR5⁺CD8⁺ T细胞的表型，并对来自TCGA的402例MIBC患者进行了生物信息学分析。研究发现，肿瘤内CXCR5⁺CD8⁺ T细胞的丰度表明总体生存率和无病生存率更高。肿瘤组织中CXCR5⁺CD8⁺ T细胞浸润较高的患者从辅助化疗（ACT）中获益更多。肿瘤内CXCR5⁺CD8⁺ T细胞表现出细胞溶解和自我更新特征。值得注意的是，CXCR5⁺CD8⁺ T细胞主要出现在MIBC的基底和富含基质的亚型中，并且富含CXCR5⁺CD8⁺ T细胞的肿瘤显示有限的FGFR3信号特征，并激活了免疫治疗和EGFR相关途径。总之，我们确定了一种具有肿瘤内CXCR5⁺CD8⁺ T细胞丰度的MIBC预后良好且对ACT敏感的亚型。CXCR5⁺CD8⁺ T细胞高密度的肿瘤对免疫治疗和EGFR靶向治疗具有潜在敏感性。CXCR5⁺CD8⁺ T细胞为MIBC提供了一种新的潜在生物标志物以及治疗靶点。
