Journal article
T cell-independent eradication of experimental glioma by intravenous TLR7/8-agonist-loaded nanoparticles
Nature communications, v 14(1), p15
11 Feb 2023
PMID: 36774352
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Glioblastoma, the most common and aggressive primary brain tumor type, is considered an immunologically "cold" tumor with sparse infiltration by adaptive immune cells. Immunosuppressive tumor-associated myeloid cells are drivers of tumor progression. Therefore, targeting and reprogramming intratumoral myeloid cells is an appealing therapeutic strategy. Here, we investigate a β-cyclodextrin nanoparticle (CDNP) formulation encapsulating the Toll-like receptor 7 and 8 (TLR7/8) agonist R848 (CDNP-R848) to reprogram myeloid cells in the glioma microenvironment. We show that intravenous monotherapy with CDNP-R848 induces regression of established syngeneic experimental glioma, resulting in increased survival rates compared with unloaded CDNP controls. Mechanistically, CDNP-R848 treatment reshapes the immunosuppressive tumor microenvironment and orchestrates tumor clearing by pro-inflammatory tumor-associated myeloid cells, independently of T cells and NK cells. Using serial magnetic resonance imaging, we identify a radiomic signature in response to CDNP-R848 treatment and ultrasmall superparamagnetic iron oxide (USPIO) imaging reveals that immunosuppressive macrophage recruitment is reduced by CDNP-R848. In conclusion, CDNP-R848 induces tumor regression in experimental glioma by targeting blood-borne macrophages without requiring adaptive immunity.
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Details
- Title
- T cell-independent eradication of experimental glioma by intravenous TLR7/8-agonist-loaded nanoparticles
- Creators
- Verena Turco - German Cancer Research CenterKira Pfleiderer - German Cancer Research CenterJessica Hunger - German Cancer Research CenterNatalie K Horvat - Tioga County Partnership for Community HealthKianush Karimian-Jazi - University Hospital HeidelbergKatharina Schregel - University Hospital HeidelbergManuel Fischer - University Hospital HeidelbergGianluca Brugnara - University Hospital HeidelbergKristine Jähne - German Cancer Research CenterVolker Sturm - University Hospital HeidelbergYannik Streibel - University Hospital HeidelbergDuy Nguyen - Heidelberg (Poland)Sandro Altamura - University Hospital HeidelbergDennis A Agardy - German Cancer Research CenterShreya S Soni - Drexel UniversityAbdulrahman Alsasa - Drexel UniversityTheresa Bunse - German Cancer Research CenterMatthias Schlesner - University of AugsburgMartina U Muckenthaler - Tioga County Partnership for Community HealthRalph Weissleder - Center for Systems BiologyWolfgang Wick - DKFZ-ZMBH AllianceSabine Heiland - University Hospital HeidelbergPhilipp Vollmuth - University Hospital HeidelbergMartin Bendszus - University Hospital HeidelbergChristopher B Rodell - Drexel UniversityMichael O Breckwoldt - German Cancer Research CenterMichael Platten - German Cancer Research Center
- Publication Details
- Nature communications, v 14(1), p15
- Publisher
- Springer Nature
- Grant note
- BR 6153/1-1 / Deutsche Forschungsgemeinschaft (German Research Foundation)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:001002560100010
- Scopus ID
- 2-s2.0-85147836434
- Other Identifier
- 991020066905104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology