التفاصيل البيبلوغرافية
| العنوان: |
Ginseng-derived nanoparticles reprogram macrophages to regulate arginase-1 release for ameliorating T cell exhaustion in tumor microenvironment |
| المؤلفون: |
Lv, Yan, Li, Mengyuan, Weng, Ling, Huang, Haoying, Mao, Yujie, Yang, Danchen Aaron, Wei, Qingyun, Zhao, Mengmeng, Wei, Qin, Rui, Ke, Han, Xuan, Fan, Weiwei, Cai, Xueting, Cao, Peng, Cao, Meng |
| المساهمون: |
the National Natural Science Foundation of China, the Natural Science Foundation of Jiangsu Province, Technology Development Program of Traditional Chinese Medicine in Jiangsu Province, WINFAST Charity Foundation, Open Project of Chinese Materia Medica First-Class Discipline of Nanjing University of Chinese Medicine, Priority Academic Program Development of Jiangsu Higher Education Institutions |
| المصدر: |
Journal of Experimental & Clinical Cancer Research ; volume 42, issue 1 ; ISSN 1756-9966 |
| بيانات النشر: |
Springer Science and Business Media LLC |
| سنة النشر: |
2023 |
| مصطلحات موضوعية: |
Cancer Research, Oncology |
| الوصف: |
Background Lines of evidence indicated that, immune checkpoints (ICs) inhibitors enhanced T cell immune response to exert anti-tumor effects. However, T cell exhaustion has been so far a major obstacle to antitumor immunotherapy in colorectal cancer patients. Our previous studies showed that ginseng-derived nanoparticles (GDNPs) inhibited the growth of various tumors by reprograming tumor-associated macrophages (TAMs) and downregulated the ICs expression on T cells in tumor microenvironment (TME), but the underlying effector mechanisms remained unclear. Methods The correlation between arginase-1 (ARG1) and T cells was computed based on the colorectal cancer patients in TCGA database. In vitro, we observed that GDNPs reprogrammed TAMs inhibited ARG1 release and ultimately ameliorated T cell exhaustion according to several techniques including WB, PCR, ELISA and flow cytometry. We also used an in vivo MC38 tumor-bearing model and administered GDNPs to assess their anti-tumor effects through multiple indices. The mechanism that GDNPs improved T cell exhaustion was further clarified using the bioinformatics tools and flow cytometry. Results GDNPs reprogramed TAMs via reducing ARG1 production. Moreover, normalized arginine metabolism ameliorated T cell exhaustion through mTOR-T-bet axis, resulting in reduced ICs expression and enhanced CD8 + T cells expansion. Conclusions By regulating the mTOR-T-bet axis, GDNPs reprogramed macrophages to regulate ARG1 release, which further ameliorated T cell exhaustion in TME. These findings provided new insights into comprehending the mechanisms underlying the mitigation of T cell exhaustion, which may facilitate the development of innovative therapeutic strategies in the field of cancer treatment. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1186/s13046-023-02888-7 |
| DOI: |
10.1186/s13046-023-02888-7.pdf |
| DOI: |
10.1186/s13046-023-02888-7/fulltext.html |
| الإتاحة: |
https://doi.org/10.1186/s13046-023-02888-7Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: |
edsbas.33417179 |
| قاعدة البيانات: |
BASE |
