articleCancer CellJan 8, 2026HYBRID OA

B cells disrupt tertiary lymphoid structure formation and suppress anti-tumor immunity

CCChanghao ChenMAMingjie AnHZHanhao ZhengMPMingrui PangPLPei Li

Sun Yat-sen University · Sun Yat-sen Memorial Hospital · +4 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Tertiary lymphoid structures (TLSs) promote antigen-specific anti-tumor immunity, but the regulators of TLSs homeostasis in cancer remain unclear. Using single-cell RNA-sequencing and spatial transcriptomics, we identify an IGLL5 + B cell subset in bladder cancer (BCa). In genetically engineered and humanized mouse models, these IGLL5 + B cells disrupt TLS's integrity and impair immunotherapy responses. Mechanistically, IGLL5 + B cells bind high endothelial venules (HEVs) via IGLL5-LTβR ligand-receptor interactions, with IGLL5 inducing a conformational change in LTβR that inhibits non-canonical NF-κB signaling, leading to TLSs disassembly. Clinically, blocking IGLL5 preserves TLSs and enhances immunotherapy…

Citation impact

8
total citations
FWCI
103.50
Percentile
100%
References
47
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Authors

17

Topics & keywords

Topics
Keywords
  • Cancer immunotherapy
  • Immunotherapy
  • Immunity
  • Cancer cell
  • Cancer
  • B cell
  • Homeostasis
  • Effector
UN Sustainable Development Goals
  • Good health and well-being
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