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

Author

Listed:
  • Verena Turco

    (German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
    Heidelberg University
    University Hospital Heidelberg)

  • Kira Pfleiderer

    (German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
    University Hospital Heidelberg)

  • Jessica Hunger

    (German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
    University Hospital Heidelberg
    Heidelberg University)

  • Natalie K. Horvat

    (Heidelberg University
    University Hospital
    Heidelberg University, European Molecular Biology Laboratory (EMBL))

  • Kianush Karimian-Jazi

    (University Hospital Heidelberg)

  • Katharina Schregel

    (University Hospital Heidelberg)

  • Manuel Fischer

    (University Hospital Heidelberg)

  • Gianluca Brugnara

    (University Hospital Heidelberg)

  • Kristine Jähne

    (German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
    Heidelberg University)

  • Volker Sturm

    (University Hospital Heidelberg)

  • Yannik Streibel

    (University Hospital Heidelberg)

  • Duy Nguyen

    (DKFZ)

  • Sandro Altamura

    (University Hospital
    Heidelberg University, European Molecular Biology Laboratory (EMBL))

  • Dennis A. Agardy

    (German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
    Heidelberg University
    Heidelberg University)

  • Shreya S. Soni

    (Drexel University)

  • Abdulrahman Alsasa

    (Drexel University)

  • Theresa Bunse

    (German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
    Heidelberg University)

  • Matthias Schlesner

    (DKFZ
    University of Augsburg)

  • Martina U. Muckenthaler

    (University Hospital
    Heidelberg University, European Molecular Biology Laboratory (EMBL))

  • Ralph Weissleder

    (Massachusetts General Hospital
    Massachusetts General Hospital and Harvard Medical School)

  • Wolfgang Wick

    (DKTK within DKFZ
    Heidelberg University Hospital)

  • Sabine Heiland

    (University Hospital Heidelberg)

  • Philipp Vollmuth

    (University Hospital Heidelberg)

  • Martin Bendszus

    (University Hospital Heidelberg)

  • Christopher B. Rodell

    (Drexel University)

  • Michael O. Breckwoldt

    (German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
    University Hospital Heidelberg)

  • Michael Platten

    (German Cancer Consortium (DKTK) within the German Cancer Research Center (DKFZ)
    Heidelberg University)

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.

Suggested Citation

  • Verena Turco & Kira Pfleiderer & Jessica Hunger & Natalie K. Horvat & Kianush Karimian-Jazi & Katharina Schregel & Manuel Fischer & Gianluca Brugnara & Kristine Jähne & Volker Sturm & Yannik Streibel , 2023. "T cell-independent eradication of experimental glioma by intravenous TLR7/8-agonist-loaded nanoparticles," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36321-6
    DOI: 10.1038/s41467-023-36321-6
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    References listed on IDEAS

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    Cited by:

    1. Zhiqi Zhang & Xiaoxuan Xu & Jiawei Du & Xin Chen & Yonger Xue & Jianqiong Zhang & Xue Yang & Xiaoyuan Chen & Jinbing Xie & Shenghong Ju, 2024. "Redox-responsive polymer micelles co-encapsulating immune checkpoint inhibitors and chemotherapeutic agents for glioblastoma therapy," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Xiaoqiong Zhang & Zhaohan Wei & Tuying Yong & Shiyu Li & Nana Bie & Jianye Li & Xin Li & Haojie Liu & Hang Xu & Yuchen Yan & Bixiang Zhang & Xiaoping Chen & Xiangliang Yang & Lu Gan, 2023. "Cell microparticles loaded with tumor antigen and resiquimod reprogram tumor-associated macrophages and promote stem-like CD8+ T cells to boost anti-PD-1 therapy," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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