ArticleJournal for immunotherapy of cancer2025
Brain tumors induce immunoregulatory dendritic cells in draining lymph nodes that can be targeted by OX40 agonist treatment.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Radiotherapy and immunotherapy in cancer treatment: mechanisms of clinical synergy.The Journal of clinical investigation · 2026Review
- Multi-omics integration and clinical validation identify CKAP2 as a diagnostic biomarker for bladder cancer.World journal of surgical oncology · 2026Article
- Single-cell omics in tumor lymph node metastasis: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- The neuro-immune-vascular landscape of lung cancer brain metastasis: insights from organoid models.Frontiers in immunology · 2026Review
- Immune Checkpoint Inhibition in Patients with Brain Metastases from Non-Small-Cell Lung Cancer: Emerging Mechanisms and Personalized Clinical Strategies.International journal of molecular sciences · 2025Review
- OX40/OX40L: a new target for tumor immunotherapy and its clinical research progress.Frontiers in oncology · 2025Review
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Authors and funding
8 authors.
Funding
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Abstract
backgroundPrimary and metastatic brain tumors have a poor prognosis, partly owing to the unique characteristics of the central nervous system (CNS) and tumor immune microenvironment (TIME). One distinct feature of the CNS TIME is the limited infiltration and activation of dendritic cells (DCs). The impact of CNS versus non-CNS TIME can be assessed by injecting tumor cells from the same model, either subcutaneously (peripherally) or into the brain. Subcutaneous tumors drain into the tumor-draining lymph nodes in the skin (TdLN-p), whereas brain tumors drain into the deep cervical TdLN (TdLN-c). We previously showed that CNS tumors that are not responsive to immune checkpoint inhibition become responsive when grown peripherally, and that non-responsiveness correlates with a tolerogenic immune response in the local TIME and TdLN-c.
methodsIn this study, we investigated the immunoregulatory potential of cervical DCs (DC-c) compared with that of peripheral DCs (DC-p) using high-resolution flow cytometry, single-cell RNA sequencing, and ex vivo and in vivo functional characterization of TdLNs from mouse models of glioma and lymphoma.
resultsOur analysis revealed that DC-c promoted regulatory T-cell expansion and poorly cytotoxic CD8
conclusionsOur findings highlight the unique immunoregulatory functions of DC-c in TdLNs and suggest the importance of OX40 signaling through direct effects on CCR7+OX40+ DCs and indirect effects on T cells.
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