B7-H4 correlates with clinical outcome and immunotherapeutic benefit in muscle-invasive bladder cancer
B7-H4 correlates with clinical outcome and immunotherapeutic benefit in muscle-invasive bladder cancer
复制标题
B7-H4 与肌层浸润性膀胱癌的临床结果和免疫治疗益处相关
DOI：
10.1016/j.ejca.2022.05.022
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发表时间：
2022-08-01
影响因子：
8.4
通讯作者：
Xu, Jiejie
中科院分区：
文献类型：
--
作者：
Liu, Zhaopei;Jin, Kaifeng;Xu, Jiejie
Aim: B7-H4, a sibling to PD-Ll in B7 family, has been reported to be a novel immune checkpoint that is prevalent among non-inflamed tumors. Herein, we attempt to explore the potential of B7-H4 in survival prediction and therapeutic guidance in muscle-invasive bladder cancer (MIBC) patients.Methods: This study included 391 patients from The Cancer Genome Atlas (TCGA) database and 122 patients from Zhongshan (ZS) Hospital. The evaluation of response to PD-Ll inhibitors was based on 270 patients in IMvigor210 cohort. Kaplan-Meier survival and multivariate analyses were performed to assess clinical outcomes in three cohorts. The correlation of B7-H4 expression with immune contexture and genomic alterations was analyzed based on immunohistochemistry, Microenvironment Cell Populations-counter (MCP-counter) tool, and whole-exome sequencing.Results: MIBC patients with the high level of B7-H4 expression (B7-H4(high)) were found to possess an inferior overall and recurrence-free survival. Nonetheless, substantial clinical benefits of cisplatin-based chemotherapy and anti-PD-L1 immunotherapy were observed in these patients. After identifying a positive correlation between B7-H4 and tumor mutation burden (TMB), clinical benefits in B7-H4(high) TMBhigh subgroup were found to be the most upon PD-L1 blockade. Further studies revealed that B7-H4(high) subgroup was featured by non-inflamed immune contexture and cell cycle-related gene alterations.Conclusions: Despite adverse clinical outcomes, B7-H4(high) patients possessed superior responsiveness to chemotherapy and immunotherapy. B7-H4 stratification could also synergize with TMB to pinpoint the patients who benefited most from immunotherapy. The clinical exploration of B7-H4 as a companion predictor could allow clinicians to direct proper therapeutic agents to patients. (C) 2022 Elsevier Ltd. All rights reserved.
