التفاصيل البيبلوغرافية
| العنوان: |
Tumor-derived exosomes drive pre-metastatic niche formation in lung via modulating CCL1+ fibroblast and CCR8+ Treg cell interactions. |
| المؤلفون: |
Wang, Ming, Qin, Zhongyu, Wan, Jiajia, Yan, Yan, Duan, Xixi, Yao, Xiaohan, Jiang, Ziming, Li, Wenqing, Qin, Zhihai |
| المصدر: |
Cancer Immunology, Immunotherapy; Nov2022, Vol. 71 Issue 11, p2717-2730, 14p |
| مصطلحات موضوعية: |
REGULATORY T cells, FIBROBLASTS, CELL populations, WESTERN immunoblotting, LUNGS |
| مستخلص: |
Background: Since the lung is one of the most common sites for cancer metastasis, it could provide a suitable microenvironment for pre-metastatic niche (PMN) formation to facilitate tumor cell colonization. Regulatory T cells (Tregs) are an immunosuppressive cell type found ubiquitously in tumors and may play a crucial role in PNM formation. In this study, we investigated tumor-derived exosome (TDE)-induced Treg differentiation in the lung PMN as well as the underlying mechanisms. Methods: TDEs were isolated from the Lewis lung carcinoma cell line (LLC-exo) and their effects on mouse pulmonary fibroblasts was investigated in vitro as well as on lung tumor formation and metastasis in a pre-injected mouse model. Immune cell populations in the lung were analyzed by flow cytometry. Expression of CCL1 and CCR8 was evaluated by immunofluorescence staining, qRT-PCR and Western blot analyses. Cytokine expression was measured using mouse cytokine arrays and ELISA. Results: The number of CD4+ FoxP3+ Tregs was significantly increased in lungs in a LLC-exo pre-injected mouse model. Lung fibroblasts secreted increased amounts of CCL1 after co-culture with LLC-exo, which induced Treg differentiation by activating its specific receptor CCR8, ultimately contributing to the establishment of an immunologically tolerant PMN. Moreover, inhibiting the release of LLC-exo by GW4869, or blocking the CCL1-CCR8 axis using AZ084, suppressed Tregs differentiation and tumor metastasis in the lung. Conclusions: Collectively, our study provides a novel mechanism by which Tregs are activated to form an immunologically tolerant PMN and demonstrates a critical link among lung fibroblasts, Tregs and metastatic tumor cells. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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