| Autor: |
Hao Chen, Anqi Qin, Fan Xu, Shuai Guo, Ge Zhang, Aihong Zhang, WenTing Li, Feng Tian, Quanhui Zheng |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Scientific Reports, Vol 14, Iss 1, Pp 1-9 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2045-2322 |
| DOI: |
10.1038/s41598-024-83447-8 |
| Popis: |
Abstract HDAC3 has been demonstrated to play a crucial role in the progression of various tumors and the differentiation and development of T cells. However, its impact on peripheral T cells in the development of murine lung cancer remains unclear. In this experiment, a subcutaneous lung tumor model was established in C57BL/6 mice, and tumor-bearing mice were treated with the specific inhibitor of HDAC3, RGFP966, at different doses to observe changes in tumor size. Additionally, a lung tumor model was established using hdac3 fl/fl cd4cre +/+ mice to investigate its mechanism. Mice injected with 10 mg/kg RGFP966 had the smallest tumor volume, while those injected with 30 mg/kg RGFP966 had the largest tumors. Flow cytometry analysis revealed that the expression of HDAC3 in splenic T cells was reduced in all groups of mice, while IFN-γ and IL-17 A were increased. Moreover, the expression of granzyme B and perforin in splenic CD8+ T cells was increased in all groups of mice. Compared to the use of 30 mg/kg RGFP966 alone, the combination with anti-IL-17 A mAb reduced the infiltration of Neutrophils and exhausted T cells in mouse tumors, thereby impeding tumor development. These findings demonstrate that the use of RGFP966 or T cell-specific loss of hdac3 promotes the expression of IL-17 A in splenic T cells, leading to tumor resistance and providing insights for clinical treatment. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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