The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours
Open accessAbstract
Immune surveillance against pathogens and tumours in the central nervous system is thought to be limited owing to the lack of lymphatic drainage. However, the characterization of the meningeal lymphatic network has shed light on previously unappreciated ways that an immune response can be elicited to antigens that are expressed in the brain1–3. Despite progress in our understanding of the development and structure of the meningeal lymphatic system, the contribution of this network in evoking a protective antigen-specific immune response in the brain remains unclear. Here, using a mouse model of glioblastoma, we show that the meningeal lymphatic vasculature can be manipulated to mount better immune responses against brain tumours. The immunity that is mediated by CD8 T cells to the glioblastoma antigen is very limited when the tumour is confined to the central nervous system, resulting in uncontrolled tumour growth. However, ectopic expression of vascular endothelial growth factor C (VEGF-C) promotes enhanced priming of CD8 T cells in the draining deep cervical lymph nodes, migration of CD8 T cells into the tumour, rapid clearance of the glioblastoma and a long-lasting antitumour memory response. Furthermore, transfection of an mRNA construct that expresses VEGF-C works synergistically with checkpoint blockade therapy to eradicate existing glioblastoma. These results reveal the capacity of VEGF-C to promote immune surveillance of tumours, and suggest a new therapeutic approach to treat brain tumours. In a mouse model of glioblastoma, treatment with VEGF-C increases lymphatic drainage in the central nervous system and improves the immune response, suggesting that modulating meningeal lymphatics could enhance checkpoint inhibitor therapy.
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Cites
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Self-citationDefining CD8+ T cells that provide the proliferative burst after PD-1 therapy
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Bolte, A. C., Dutta, A. B., Hurt, M. E., Smirnov, I., Kovacs, M. A., McKee, C. A., Ennerfelt, H. E., Shapiro, D., Nguyen, B. H., Frost, E. L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18113-4 · Cited by 357
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Rustenhoven, J., & Kipnis, J. (2022) · Nature · doi:10.1038/s41586-022-05474-7 · Cited by 253
Nanomedicine-Based Approaches for mRNA Delivery
Uchida, S., Perche, F., Pichon, C., & Cabral, H. (2020) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.0c00618 · Cited by 139
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Metadata
- Authors
- Song, E., Mao, T., Dong, H., Boisserand, L. S. B., Antila, S., Bosenberg, M., Alitalo, K., Thomas, J.-L., & Iwasaki, A.
- Venue
- Nature
- Published
- 2020-01-15
- Volume
- 577
- Issue
- 7792
- Pages
- 689-694
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3000438116
- Cited by
- 532
- References
- 34
- FWCI
- 24.46
- Type
- journal article
- Language
- en
- Open access
- green
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- Song, E., Mao, T., Dong, H., Boisserand, L. S. B., Antila, S., Bosenberg, M., Alitalo, K., Thomas, J.-L., & Iwasaki, A. (2020). VEGF-C-driven lymphatic drainage enables immunosurveillance of brain tumours. Nature. https://doi.org/10.1038/s41586-019-1912-x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
