ArticleNeuro-oncology2025
Toll-like receptor agonists promote the formation of tertiary lymphoid structure and improve anti-glioma immunity.
Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Niches in cancer: from primary tumors to metastatic disease.Journal of hematology & oncology · 2026Review
- CD8⁺ T Cell infiltration and spatial organization in cancer: mechanisms, barriers, and therapeutic strategies.Molecular biomedicine · 2026Review
- Harnessing Natural Killer Cells: From Neuroimmunology to Novel Therapies for Central Nervous System Diseases.MedComm · 2026Review
- B cells in cancer: functions, mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- TLS as Predictors and Targets in Neoadjuvant Chemoimmunotherapy for NSCLC.Thoracic cancer · 2026Review
- TCF1+CD4+ T cells and microglia co-orchestrate tertiary lymphoid structures to enhance prognosis and immunotherapy in non-small cell lung cancer with brain metastases.EBioMedicine · 2026Article
- scComm: a contrastive learning framework for deciphering cell-cell communications at single-cell resolution.Genome biology · 2026Article
- CD19Breast cancer research : BCR · 2026Article
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Artery Tertiary Lymphoid Organs Form Neuroimmune Cardiovascular Interfaces in Atherosclerosis.Immunological reviews · 2026Review
- Tertiary lymphoid structure can be a potential therapeutic target for head and neck squamous cell carcinoma (Review).Molecular and clinical oncology · 2026Review
- Initiation of Tertiary Lymphoid Structures for Cancer Immunotherapy.Research (Washington, D.C.) · 2026Review
- Tertiary lymphoid structures in cancer: spatiotemporal heterogeneity, immune orchestration, and translational opportunities.Journal of hematology & oncology · 2025Review
- The roles of tertiary lymphoid structures in orchestrating immune responses in peripheral organs.Inflammation and regeneration · 2025Review
- Dynamic remodeling of tertiary lymphoid structures in response to cancer therapy: a recent review.Cancer immunology, immunotherapy : CII · 2025Review
- TP63 as a modulator of ferroptosis in TP53 mutations glioblastoma.Cell death & disease · 2025Article
- Emerging role of follicular regulatory T-cells in neuroimmunological disorders.Current opinion in immunology · 2025Review
- Toll-Like Receptors in the Immunotherapy Era: Dual-Edged Swords of Tumor Immunity and Clinical Translation.MedComm · 2025Review
- Exploring the tumor microenvironment in diffuse intrinsic pontine glioma: immunological insights and therapeutic challenges.Journal for immunotherapy of cancer · 2025Review
- Tertiary lymphoid structures in gliomas: impact on tumour immunity and progression.Journal of translational medicine · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
backgroundGlioma, characterized by limited lymphocytic infiltration, constitutes an "immune-desert" tumor displaying insensitivity to various immunotherapies. This study aims to explore therapeutic strategies for inducing tertiary lymphoid structure (TLS) formation within the glioma microenvironment (GME) to transition it from an immune resistant to an activated state.
methodsTLS formation in GME was successfully induced by intracranial administration of Toll-like receptor (TLR) agonists (OK-432, TLR2/4/9 agonist) and glioma antigens (i.c. αTLR-mix). We employed staining analysis, antibody neutralization, single-cell RNA sequencing (scRNA-Seq), and BCR/TCR sequencing to investigate the underlying mechanisms of TLS formation and its role in anti-glioma immunity. Additionally, a preliminary translational clinical study was conducted.
resultsTLS formation correlated with increased lymphocyte infiltration in GME and led to improved prognosis in glioma-bearing mice. In the study of TLS induction mechanisms, certain macrophages/microglia and Th17 displayed markers of "LTo" and "LTi" cells, respectively, interaction through LTα/β-LTβR promoted TLS induction. Post-TLS formation, CD4 + and CD8 + T cells but not CD19 + B cells contributed to anti-glioma immunity. Comparative analysis of B/T cells between brain and lymph node showed that brain B/T cells unveiled the switch from naïve to mature, some B cells highlighted an enrichment of class switch recombination (CSR)-associated genes, V gene usage, and clonotype bias were observed. In related clinical studies, i.c. αTLR-mix treatment exhibited tolerability, and chemokines/cytokines assay provided preliminary evidence supporting TLS formation in GME.
conclusionsTLS induction in GME enhanced anti-glioma immunity, improved the immune microenvironment, and controlled glioma growth, suggesting potential therapeutic avenues for treating glioma in the future.
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