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T cell-independent eradication of experimental glioma by intravenous TLR7/8-agonist-loaded nanoparticles by Verena Turco; Kira Pfleiderer; Jessica Hunger; Natalie K. Horvat; Kianush Karimian-Jazi; Katharina Schregel; Manuel Fischer; Gianluca Brugnara; Kristine Jähne; Volker Sturm; Yannik Streibel; Duy Nguyen; Sandro Altamura; Dennis A. Agardy; Shreya S. Soni; Abdulrahman Alsasa; Theresa Bunse; Matthias Schlesner; Martina U. Muckenthaler; Ralph Weissleder; Wolfgang Wick; Sabine Heiland; Philipp Vollmuth; Martin Bendszus; Christopher B. Rodell; Michael O. Breckwoldt; Michael Platten is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is T cell-independent eradication of experimental glioma by intravenous TLR7/8-agonist-loaded nanoparticles about?

## 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 recruit

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Author

Verena Turco; Kira Pfleiderer; Jessica Hunger; Natalie K. Horvat; Kianush Karimian-Jazi; Katharina Schregel; Manuel Fischer; Gianluca Brugnara; Kristine Jähne; Volker Sturm; Yannik Streibel; Duy Nguyen; Sandro Altamura; Dennis A. Agardy; Shreya S. Soni; Abdulrahman Alsasa; Theresa Bunse; Matthias Schlesner; Martina U. Muckenthaler; Ralph Weissleder; Wolfgang Wick; Sabine Heiland; Philipp Vollmuth; Martin Bendszus; Christopher B. Rodell; Michael O. Breckwoldt; Michael Platten

Publisher

Springer Science and Business Media LLC

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)