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Open Access 01-12-2024 | Interferon | Research

Single-cell sequencing reveals the heterogeneity of B cells and tertiary lymphoid structures in muscle-invasive bladder cancer

Authors: Hao Yuan, Xingning Mao, Yunkun Yan, Rong Huang, Qingyun Zhang, Yanyu Zeng, Mengying Bao, Yan Dai, Bo Fang, Junhao Mi, Yuli Xie, Xiang Wang, Haiying Zhang, Zengnan Mo, Rirong Yang

Published in: Journal of Translational Medicine | Issue 1/2024

Abstract

Background

Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease with a poor prognosis. B cells are crucial factors in tumor suppression, and tertiary lymphoid structures (TLSs) facilitate immune cell recruitment to the tumor microenvironment (TME). However, the function and mechanisms of tumor-infiltrating B cells and TLSs in MIBC need to be explored further.

Methods

We performed single-cell RNA sequencing analysis of 11,612 B cells and 55,392 T cells from 12 bladder cancer patients and found naïve B cells, proliferating B cells, plasma cells, interferon-stimulated B cells and germinal center-associated B cells, and described the phenotype, gene enrichment, cell–cell communication, biological processes. We utilized immunohistochemistry (IHC) and immunofluorescence (IF) to describe TLSs morphology in MIBC.

Results

The interferon-stimulated B-cell subtype (B-ISG15) and germinal center-associated B-cell subtypes (B-LMO2, B-STMN1) were significantly enriched in MIBC. TLSs in MIBC exhibited a distinct follicular structure characterized by a central region of B cells resembling a germinal center surrounded by T cells. CellChat analysis showed that CXCL13 + T cells play a pivotal role in recruiting CXCR5 + B cells. Cell migration experiments demonstrated the chemoattraction of CXCL13 toward CXCR5 + B cells. Importantly, the infiltration of the interferon-stimulated B-cell subtype and the presence of TLSs correlated with a more favorable prognosis in MIBC.

Conclusions

The study revealed the heterogeneity of B-cell subtypes in MIBC and suggests a pivotal role of TLSs in MIBC outcomes. Our study provides novel insights that contribute to the precision treatment of MIBC.

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Title: Single-cell sequencing reveals the heterogeneity of B cells and tertiary lymphoid structures in muscle-invasive bladder cancer
Authors: Hao Yuan
Xingning Mao
Yunkun Yan
Rong Huang
Qingyun Zhang
Yanyu Zeng
Mengying Bao
Yan Dai
Bo Fang
Junhao Mi
Yuli Xie
Xiang Wang
Haiying Zhang
Zengnan Mo
Rirong Yang
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Interferon
Published in: Journal of Translational Medicine / Issue 1/2024
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-024-04860-1

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