DataVXAdvanced MaterialsPaper
journal article·2024-11

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

Lei Dong, Yini Zhu, Haoge Zhang, Lin Gao, Zhiqi Zhang, Xiaoxuan Xu, Leqian Ying, Lu Zhang, Yue Li, Zhengcheng Yun, Danqi Zhu, Chang Han, Tingting Xu, Hui Yang, Shenghong Ju, Xiaoyuan Chen, Haijun Zhang, Jinbing Xie

Advanced Materials· Volume 36· Issue 44
Publisher page
Source abstract

Abstract

Abstract 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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: CAR-T cell therapy research · Nanoplatforms for cancer theranostics · Immunotherapy and Immune Responses

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology; Department of Oncology Zhongda Hospital Medical School Southeast University 87 Dingjiaqiao Nanjing 210009 China

Department of Microbiology and Immunology Medical School of Southeast University Nanjing Jiangsu 210009 China

Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology Basic Medicine Research and Innovation Center of Ministry of Education State Key Laboratory of Digital Medical Engineering Department of Radiology Zhongda Hospital Medical School of Southeast University Nanjing 210009 China

State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau Macau SAR 999078 China

Department of Biochemistry and Molecular Biology Medical School of Southeast University Nanjing China

Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering Yong Loo Lin School of Medicine and College of Design and Engineering National University of Singapore Singapore 119074 Singapore

Nanomedicine Translational Research Program NUS Center for Nanomedicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore

Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117599 Singapore

Institute of Molecular and Cell Biology Agency for Science Technology, and Research (A*STAR) 61 Biopolis Drive, Proteos Singapore 138673 Singapore

Funding

National Natural Science Foundation of China · National Key Research and Development Program of China

References (53)

Show source-provided references
1. 10.3322/caac.2169310.3322/caac.21693 ↗
2. 10.1136/jnnp-2020-32533410.1136/jnnp-2020-325334 ↗
3. 10.1016/j.cell.2023.02.03910.1016/j.cell.2023.02.039 ↗
4. 10.1158/1078-0432.CCR-20-330510.1158/1078-0432.CCR-20-3305 ↗
5. 10.1172/JCI16344710.1172/JCI163447 ↗
6. 10.1016/j.immuni.2024.02.00110.1016/j.immuni.2024.02.001 ↗
7. 10.1002/adma.20220978510.1002/adma.202209785 ↗
8. 10.1016/j.it.2023.09.00310.1016/j.it.2023.09.003 ↗
9. 10.1038/s41423-021-00786-610.1038/s41423-021-00786-6 ↗
10. 10.1186/s13046-022-02349-710.1186/s13046-022-02349-7 ↗
11. 10.1001/jama.2023.002310.1001/jama.2023.0023 ↗
12. 10.1073/pnas.230697312110.1073/pnas.2306973121 ↗
13. 10.1002/adma.20231110910.1002/adma.202311109 ↗
14. 10.1016/j.addr.2022.11458310.1016/j.addr.2022.114583 ↗
15. 10.1016/j.actbio.2021.09.01010.1016/j.actbio.2021.09.010 ↗
16. 10.1016/j.jconrel.2023.08.06010.1016/j.jconrel.2023.08.060 ↗
17. 10.1016/j.immuni.2021.11.00210.1016/j.immuni.2021.11.002 ↗
18. 10.1016/j.canlet.2023.21626310.1016/j.canlet.2023.216263 ↗
19. 10.1038/s41571-022-00689-z10.1038/s41571-022-00689-z ↗
20. 10.1016/j.jconrel.2021.12.00510.1016/j.jconrel.2021.12.005 ↗
21. 10.1016/j.addr.2022.11453910.1016/j.addr.2022.114539 ↗
22. 10.1002/adma.20231042110.1002/adma.202310421 ↗
23. 10.1002/adma.20170711310.1002/adma.201707113 ↗
24. Li T. · J Control Release · 2015 · 213
25. 10.1016/j.addr.2021.11384710.1016/j.addr.2021.113847 ↗
26. 10.1186/s12951-022-01243-w10.1186/s12951-022-01243-w ↗
27. 10.1016/j.biomaterials.2014.02.03610.1016/j.biomaterials.2014.02.036 ↗
28. 10.1038/s41467-024-45818-710.1038/s41467-024-45818-7 ↗
29. 10.1172/JCI14854610.1172/JCI148546 ↗
30. 10.1016/j.immuni.2021.08.01910.1016/j.immuni.2021.08.019 ↗
31. 10.1016/j.trecan.2022.09.00510.1016/j.trecan.2022.09.005 ↗
32. 10.1016/j.ultsonch.2023.10660810.1016/j.ultsonch.2023.106608 ↗
33. 10.1016/j.jconrel.2022.03.03510.1016/j.jconrel.2022.03.035 ↗
34. 10.1016/j.ultsonch.2022.10626110.1016/j.ultsonch.2022.106261 ↗
35. 10.1016/j.bbcan.2023.18891310.1016/j.bbcan.2023.188913 ↗
36. 10.1126/sciadv.add228810.1126/sciadv.add2288 ↗
37. 10.1073/pnas.180710511510.1073/pnas.1807105115 ↗
38. 10.1021/acssensors.2c0146810.1021/acssensors.2c01468 ↗
39. 10.1002/adma.20220324610.1002/adma.202203246 ↗
40. 10.1038/s41467-023-42509-710.1038/s41467-023-42509-7 ↗
41. 10.1016/j.jconrel.2024.01.03410.1016/j.jconrel.2024.01.034 ↗
42. 10.1126/sciadv.aay134410.1126/sciadv.aay1344 ↗
43. 10.1038/s41568-023-00560-y10.1038/s41568-023-00560-y ↗
44. 10.1016/j.ccell.2022.02.00310.1016/j.ccell.2022.02.003 ↗
45. 10.1038/s41577-021-00574-310.1038/s41577-021-00574-3 ↗
46. 10.1038/s41577-021-00537-810.1038/s41577-021-00537-8 ↗
47. 10.1016/j.canlet.2022.21604310.1016/j.canlet.2022.216043 ↗
48. 10.1038/s41392-023-01471-y10.1038/s41392-023-01471-y ↗
49. 10.1084/jem.2020160510.1084/jem.20201605 ↗
50. 10.1038/s41467-021-21022-910.1038/s41467-021-21022-9 ↗
51. 10.1002/adma.20230815010.1002/adma.202308150 ↗
52. 10.1016/j.addr.2021.11404310.1016/j.addr.2021.114043 ↗
53. 10.1158/1078-0432.CCR-20-376010.1158/1078-0432.CCR-20-3760 ↗