Evidence map›Paper›PMID 40437466›Full record

ArticleBMC cancer2025

Toll-like receptor 9 (TLR9) expression correlates with cell of origin and predicts clinical outcome in diffuse large B-cell lymphoma.

Sulaf Abd Own, Ioanna Xagoraris, Konstantina Stathopoulou, Björn E Wahlin, Weicheng Ren, Mehran Ghaderi, Qiang Pan-Hammarström, Birgitta Sander, Karin E Smedby, Georgios Rassidakis

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Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Sulaf Abd OwnDepartment of Medicine Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden. Sulaf.abd.own@ki.se.
Ioanna XagorarisDepartment of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, 141 86, Sweden.
Konstantina StathopoulouDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Björn E WahlinDepartment of Hematology, Karolinska University, Hospital Solna, Stockholm, Sweden.
Weicheng RenDepartment of Medical Biochemistry and Biophysics, Division of Immunology, Karolinska Institutet, Stockholm, Sweden.
Mehran GhaderiDepartment of Laboratory Medicine, Division of Pathology, Karolinska Institutet and Karolinska University Hospital, Stockholm, 14186, Sweden.
Qiang Pan-HammarströmDepartment of Medical Biochemistry and Biophysics, Division of Immunology, Karolinska Institutet, Stockholm, Sweden.
Birgitta Sander *Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, 141 86, Sweden.
Karin E Smedby *Department of Medicine Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
Georgios Rassidakis *Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, 141 86, Sweden.

Funding

Swedish Cancer Society 23 2846 Pj
6 · The paper itself

Abstract

backgroundBiological insights beyond the cell-of-origin (COO) classification can support clinical management in diffuse large B-cell lymphoma (DLBCL). We investigated if Toll-like receptor 9 (TLR9) expression could serve as a prognostic marker in DLBCL.

methodTLR9 gene expression was analysed in four publicly available cohorts (n = 2474), and protein expression was investigated in germinal centre B-cell (GCB) and activated B-cell (ABC) DLBCL cell lines. Next, TLR9 protein expression was analysed in 120 diagnostic samples from R-CHOP-treated patients with relapsed/refractory disease (poor outcome, n = 50) or in complete remission (good outcome, n = 70). Associations were evaluated using logistic regression, estimating odds ratios (OR) and 95% confidence intervals (CI).

resultsTLR9 gene expression was higher in ABC DLBCL compared to GCB DLBCL in external cohorts, and similar results were obtained for protein expression in cell lines. In patient samples, high TLR9 protein expression correlated with non-GCB type (p = 0.003) and poor outcome (p = 0.0016). High TLR9 expression remained associated with poor outcome in multivariable analysis after adjusting for COO and other clinical features (OR = 3.36, 95% CI 1.41-8.04). In exploratory analyses, a decrease of cell growth in ABC cell lines following inhibition of TLR9 activity with ODN4084-F was suggested.

conclusionWe conclude that TLR9 correlates with ABC/non-GCB phenotype and is a potential predictor of poor prognosis in DLBCL.

Indexed as

Biomarkers, TumorLymphoma, Large B-Cell, DiffuseToll-Like Receptor 9AdultAgedAntineoplastic Combined Chemotherapy ProtocolsB-LymphocytesCell Line, TumorCyclophosphamideDoxorubicinFemaleGene Expression Regulation, NeoplasticGerminal CenterHumansMaleMiddle AgedBiomarkers, TumorCyclophosphamideDoxorubicinPrednisoneR-CHOP protocolRituximabTLR9 protein, humanToll-Like Receptor 9VincristineBiomarkerDLBCLPrognosisTLR9

Identifiers

PMID40437466
PMCPMC12117956

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