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Cancer Immunology, Immunotherapy

, Volume 68, Issue 1, pp 45–56 | Cite as

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

  • Qi Jiang
  • Qiang Fu
  • Yuan Chang
  • Zheng Liu
  • Junyu Zhang
  • Le Xu
  • Yu Zhu
  • Yiwei Wang
  • Weijuan ZhangEmail author
  • Jiejie XuEmail author
Original Article
  • 189 Downloads

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.

Keywords

CD19+ TIB Muscle-invasive bladder cancer Adjuvant chemotherapy Antitumor response 

Abbreviations

ACT

Adjuvant chemotherapy

CD19+ TIB

CD19+ tumor-infiltrating B-cell(s)

GSEA

Gene set enrichment analysis

MIBC

Muscle-invasive bladder cancer

RC

Radical cystectomy

TCGA

The Cancer Genome Atlas

TIT

Tumor-infiltrating T-cell(s)

TMA

Tissue microarray

Notes

Author contributions

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.

Funding

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.

Supplementary material

262_2018_2250_MOESM1_ESM.pdf (433 kb)
Supplementary material 1 (PDF 432 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Immunology, School of Basic Medical SciencesFudan UniversityShanghaiChina
  2. 2.Department of Biochemistry and Molecular Biology, School of Basic Medical SciencesFudan UniversityShanghaiChina
  3. 3.Department of UrologyFudan University Shanghai Cancer CenterShanghaiChina
  4. 4.Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
  5. 5.Department of Urology, Ruijin Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
  6. 6.Department of Urology, Ninth People’s Hospital, School of MedicineShanghai Jiaotong UniversityShanghaiChina

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