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B7-H4 correlates with clinical outcome and immunotherapeutic benefit in muscle-invasive bladder cancer.
- Source :
-
European Journal of Cancer . Aug2022, Vol. 171, p133-142. 10p. - Publication Year :
- 2022
-
Abstract
- B7-H4, a sibling to PD-L1 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. 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-L1 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. MIBC patients with the high level of B7-H4 expression (B7-H4high) 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-H4high TMBhigh subgroup were found to be the most upon PD-L1 blockade. Further studies revealed that B7-H4high subgroup was featured by non-inflamed immune contexture and cell cycle-related gene alterations. Despite adverse clinical outcomes, B7-H4high 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. • B7-H4 expression was proved to be an adverse prognosticator in MIBC. • B7-H4high patients had prolonged survival after chemotherapy or immunotherapy. • B7-H4high TMBhigh patients might benefit most from PD-L1 blockade. • B7-H4 correlated with non-inflamed immune contexture in MIBC. [ABSTRACT FROM AUTHOR]
- Subjects :
- *IMMUNE checkpoint inhibitors
*IMMUNE checkpoint proteins
*SEQUENCE analysis
*IMMUNOHISTOCHEMISTRY
*CANCER chemotherapy
*TREATMENT effectiveness
*CANCER patients
*KAPLAN-Meier estimator
*SURVIVAL analysis (Biometry)
*DESCRIPTIVE statistics
*CISPLATIN
*TUMOR markers
*IMMUNOTHERAPY
*EVALUATION
BLADDER tumors
Subjects
Details
- Language :
- English
- ISSN :
- 09598049
- Volume :
- 171
- Database :
- Academic Search Index
- Journal :
- European Journal of Cancer
- Publication Type :
- Academic Journal
- Accession number :
- 157993222
- Full Text :
- https://doi.org/10.1016/j.ejca.2022.05.022