Open-Source Throttling of CD8+ T Cells in Brain with Low-Intensity Focused Ultrasound-Guided Sequential Delivery of CXCL10, IL-2, and aPD-L1 for Glioblastoma Immunotherapy

Open-Source Throttling of CD8+ T Cells in Brain with Low-Intensity Focused Ultrasound-Guided Sequential Delivery of CXCL10, IL-2, and aPD-L1 for Glioblastoma Immunotherapy

© 2024 Wiley‐VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 44 vom: 25. Nov., Seite e2407235
1. Verfasser: Dong, Lei (VerfasserIn)
Weitere Verfasser: Zhu, Yini, Zhang, Haoge, Gao, Lin, Zhang, Zhiqi, Xu, Xiaoxuan, Ying, Leqian, Zhang, Lu, Li, Yue, Yun, Zhengcheng, Zhu, Danqi, Han, Chang, Xu, Tingting, Yang, Hui, Ju, Shenghong, Chen, Xiaoyuan, Zhang, Haijun, Xie, Jinbing
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article CXCL10 IL‐2 T‐cell exhaustion glioblastoma immune checkpoint inhibitors immunosuppressive microenvironment low‐frequency focused ultrasound B7-H1 Antigen Chemokine CXCL10 Interleukin-2
Beschreibung
Zusammenfassung:© 2024 Wiley‐VCH GmbH.
Improving clinical immunotherapy for glioblastoma (GBM) relies on addressing the immunosuppressive tumor microenvironment (TME). Enhancing CD8+ T cell infiltration and preventing its exhaustion holds promise for effective GBM immunotherapy. Here, a low-intensity focused ultrasound (LIFU)-guided sequential delivery strategy is developed to enhance CD8+ T cells infiltration and activity in the GBM region. The sequential delivery of CXC chemokine ligand 10 (CXCL10) to recruit CD8+ T cells and interleukin-2 (IL-2) to reduce their exhaustion is termed an "open-source throttling" strategy. Consequently, up to 3.39-fold of CD8+ T cells are observed with LIFU-guided sequential delivery of CXCL10, IL-2, and anti-programmed cell death 1 ligand 1 (aPD-L1), compared to the free aPD-L1 group. The immune checkpoint inhibitors (ICIs) therapeutic efficacy is substantially enhanced by the reversed immunosuppressive TME due to the expansion of CD8+ T cells, resulting in the elimination of tumor, prolonged survival time, and long-term immune memory establishment in orthotopic GBM mice. Overall, LIFU-guided sequential cytokine and ICIs delivery offers an "open-source throttling" strategy of CD8+ T cells, which may present a promising strategy for brain-tumor immunotherapy
Beschreibung:Date Completed 01.11.2024
Date Revised 07.11.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.202407235