CD8+ T effector and immune checkpoint signatures predict prognosis and responsiveness to immunotherapy in bladder cancer

被引：72

作者：

Chen, Xingyu ^{[1
]}

Xu, Runshi ^{[2
]}

He, Dong ^{[3
]}

Zhang, Yao ^{[1
]}

Chen, Haotian ^{[1
]}

Zhu, Yuxing ^{[1
]}

Cheng, YaXin ^{[1
]}

Liu, Rui ^{[1
]}

Zhu, Rongrong ^{[1
]}

Gong, Lian ^{[1
]}

Xiao, Mengqing ^{[1
]}

Wang, Zhanwang ^{[1
]}

Deng, Liping ^{[1
]}

Cao, Ke ^{[1
]}

机构：

[1] Cent South Univ, Xiangya Hosp 3, Dept Oncol, 283 Tongzipo Rd, Changsha 410013, Peoples R China

[2] Hunan Univ Chinese Med, Med Sch, 300 Xueshi Rd,Hanpu Kejiao Pk, Changsha 410208, Peoples R China

[3] Hunan Univ Chinese Med, Peoples Hosp Hunan Prov 2, Dept Resp, Changsha 410000, Peoples R China

来源：

ONCOGENE | 2021年 / 40卷 / 43期

基金：

中国国家自然科学基金;

关键词：

CXCL13;

D O I：

10.1038/s41388-021-02019-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Immune-checkpoint blockade (ICB) has been routinely implemented to treat bladder cancer; however, most patients have little or no clinical benefit. In this study, 348 pretreated metastatic urothelial cancer samples from the IMvigor210 cohort were used to identify important genes significantly associated with CD8+ T effector and immune checkpoint signatures. The immune checkpoint inhibitor score (IMS) scoring system was constructed to predict the immunotherapy responsiveness. Transcriptome analysis confirmed that the high IMS score group had significant immune activation with better prognosis and higher immunotherapy responsiveness, which was a powerful biomarker for predicting the prognosis and responsiveness of ICB. Tumor immune dysfunction and exclusion (TIDE) scores were calculated using 2031 external bladder cancer samples for further validation. We selected the important Hub genes as potential therapeutic targets, and validated the genes using genomic, transcriptomic, immunomic, and other multi-omics methods. In addition, we construct a risk prediction model which could stratify patients with bladder cancer and predict patient prognosis and ICB treatment responsiveness. In conclusion, this study identified effective biomarkers for the prediction of immune checkpoint inhibitor treatment responsiveness in bladder cancer patients and provided new immunotherapeutic targets.

引用

页码：6223 / 6234

页数：12

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