CD19 + tumor-infiltrating B-cells prime CD4 + T-cell immunity and predict platinum-based chemotherapy efficacy in muscle-invasive bladder cancer

Abstract

Purpose

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.

Experimental design

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.

Results

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.

Conclusion

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.

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