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Omics · study · 2026

Morphological and Single-Cell Analyses of En Bloc Resected Non-Muscle invasive Bladder Cancer Reveal Structural and functional disruption of Tertiary lymphoid Structures

Listed in NCBI GEO

Tertiary lymphoid structures (TLS) have emerged as critical immune niches within the tumor microenvironment across various cancers.

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However, their structural organization and functional roles in non–muscle-invasive bladder cancer (NMIBC) remain poorly characterized. In this study, we provide the first detailed characterization of TLS in NMIBC using en bloc resected specimens, enabling high-resolution spatial mapping and quantitative histological assessment across a large cohort of primary tumors (n=97).

Compared with TLS in inflammation-driven cystitis, tumor-associated TLS showed heterogeneous spatial organization, altered immune composition, and less structured follicular dendritic cell (FDC) networks with reduced high endothelial venule density (p<0.0001). TLS density increased with NMIBC grade and stage (p=0.01) and was associated with greater recurrence risk and shorter progression-free survival in high-TLS tumors (p=0.004).

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In paired primary and recurrent tumors (n=16), TLS showed progressive FDC disorganization and M2 macrophage polarization, supporting their role in shaping an immunosuppressive microenvironment. Single-cell RNA sequencing of TLS from NMIBC and cystitis samples revealed impaired germinal center activity in tumor-associated TLS, with asynchronous B cell maturation and reduced B cell interactions with both T follicular helper and FDC (p<0.0001).

They also showed increased myeloid infiltration and altered dendritic cell function, including reduced MHC class II antigen presentation and downregulation of co-stimulatory (CD86–CD28) and migration-related (CD99) pathways compared to cystitis (p<0.0001). Overall, NMIBC-associated TLS are structurally and functionally impaired, which may limit effective local immune responses and highlights their potential as biomarkers and targets for immunomodulatory therapy in bladder cancer

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Life Sciences
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Cancer 75% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 11 field assertions
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NCBI GEOGSE31080215 d agoJSON v1
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concepts[modality].local:modality:rna-seqenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
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