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

Authors :
Jiang, Qi
Fu, Qiang
Chang, Yuan
Liu, Zheng
Zhang, Junyu
Xu, Le
Zhu, Yu
Wang, Yiwei
Zhang, Weijuan
Xu, Jiejie
Source :
Cancer Immunology, Immunotherapy; Jan2019, Vol. 68 Issue 1, p45-56, 12p
Publication Year :
2019

Abstract

Purpose: CD19<superscript>+</superscript> tumor-infiltrating B-cells (CD19<superscript>+</superscript> 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<superscript>+</superscript> 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<superscript>+</superscript> TIB. The mechanism underlying CD19<superscript>+</superscript> TIB antitumor immunity was explored through the Cancer Genome Atlas (TCGA) dataset analysis and an in vitro Ag presentation assay.Results: CD19<superscript>+</superscript> TIB extensively infiltrated into the tumor stroma of MIBC. Adjuvant chemotherapy (ACT) led to a significantly increased benefit in the high CD19<superscript>+</superscript> TIB MIBC patients (P = 0.003). In multivariate analysis, high CD19<superscript>+</superscript> 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<superscript>+</superscript> TIB MIBC patients. Moreover, CD19<superscript>+</superscript> TIB co-localized with activated CD4<superscript>+</superscript> TIT and expressed surface markers characteristic of antigen-presenting cells. Finally, an antigen-presentation assay demonstrated the antigen-presentation function of CD19<superscript>+</superscript> TIB.Conclusion: CD19<superscript>+</superscript> TIB was identified as an independent prognostic factor, which could predict for post-surgery survival and platinum-based ACT benefits in MIBC. CD19<superscript>+</superscript> TIB serve as antigen-presenting cells (APCs) to activate CD4<superscript>+</superscript> TIT in the tumor environment of MIBC. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
03407004
Volume :
68
Issue :
1
Database :
Complementary Index
Journal :
Cancer Immunology, Immunotherapy
Publication Type :
Academic Journal
Accession number :
134058398
Full Text :
https://doi.org/10.1007/s00262-018-2250-9