CD19+ tumor-infiltrating B-cells prime CD4+ T-cell immunity and predict platinum-based chemotherapy efficacy in muscle-invasive bladder cancer
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CD19+ tumor-infiltrating B-cells (CD19+ TIB) play a crucial role in tumorigenesis, but their clinical relevance in muscle-invasive bladder cancer (MIBC) remains unknown. This study aimed to investigate the prognostic value of CD19+ TIB for post-surgery survival and adjuvant chemotherapy response in MIBC.
We assessed TIB by immunohistochemical staining of CD19 in 246 MIBC patients from Zhongshan Hospital and Shanghai Cancer Center. We evaluated the survival benefit of platinum-based chemotherapy according to CD19+ TIB. The mechanism underlying CD19+ TIB antitumor immunity was explored through the Cancer Genome Atlas (TCGA) dataset analysis and an in vitro Ag presentation assay.
CD19+ TIB extensively infiltrated into the tumor stroma of MIBC. Adjuvant chemotherapy (ACT) led to a significantly increased benefit in the high CD19+ TIB MIBC patients (P = 0.003). In multivariate analysis, high CD19+ TIB MIBC patients had significantly longer OS with ACT in the discovery set (HR = 0.487, P = 0.038). TCGA gene expression analyses showed enrichment of adaptive immunity, T-cell-mediated immunity, and antigen-presentation signaling pathways in high CD19+ TIB MIBC patients. Moreover, CD19+ TIB co-localized with activated CD4+ TIT and expressed surface markers characteristic of antigen-presenting cells. Finally, an antigen-presentation assay demonstrated the antigen-presentation function of CD19+ TIB.
CD19+ TIB was identified as an independent prognostic factor, which could predict for post-surgery survival and platinum-based ACT benefits in MIBC. CD19+ TIB serve as antigen-presenting cells (APCs) to activate CD4+ TIT in the tumor environment of MIBC.
KeywordsCD19+ TIB Muscle-invasive bladder cancer Adjuvant chemotherapy Antitumor response
- CD19+ TIB
CD19+ tumor-infiltrating B-cell(s)
Gene set enrichment analysis
Muscle-invasive bladder cancer
The Cancer Genome Atlas
QJ, QF and YC: acquisition of data, analysis and interpretation of data, statistical analysis and drafting the manuscript. ZL, JZ, LX, YZ and YW: technical and material support. WZ and JX: study concept and design, analysis and interpretation of data, drafting the manuscript, obtained the funding and study supervision. All authors read and approved the final manuscript.
This study was funded by grants from the National Natural Science Foundation of China (81471621, 81472227, 81671628, 31770851, 81871306 and 81872082), the Shanghai Municipal Natural Science Foundation (17ZR1405100), the Shanghai Sailing Program (18YF1404500) and the Shanghai Municipal Commission of Health and Family Planning Program (20144Y0223). The study sponsors had no roles in the study design or in the collection, analysis, and interpretation of data.
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
Ethical approval and ethical standards
This study was approved by the institutional ethical review boards of Zhongshan Hospital, Fudan University (Registration no. B2015-030) and Fudan University Shanghai Cancer Center (Registration no. 050432-4-1212B). Written informed consent approved by the institutional ethics committee was obtained from each patient.
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