| Autor: |
Meifang Xu, Fei Wang, Hong Chen, Lin Liu, Wenwen Liu, Yinghong Yang, Qiaoling Zheng, Lihong Zhang, Xiaoxuan Li, Suxia Lin, Shengbing Zang |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Cancer Biology & Medicine, Vol 16, Iss 4, Pp 743-755 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2095-3941 |
| DOI: |
10.20892/j.issn.2095-3941.2019.0115 |
| Popis: |
ObjectiveAngioimmunoblastic T cell lymphoma (AITL) is an aggressive form of non-Hodgkin lymphoma derived from mature T cells. However, the underlying pathogenesis of AITL remains unresolved. We aimed to explore the role of FOXO1-mediated signaling in the tumorigenesis and progression of AITL.MethodsFOXO1 expression was assessed using immunohistochemistry on a total of 46 AITL tissue samples. Retroviruses encoding FOXO1 shRNA were used to knockdown FOXO1 expression in CD4+ T cells. Flow cytometric assays analyzed the proliferation and survival of FOXO1 knockdown CD4+ T cells. Furthermore, we performed adoptive T-cell transfer experiments to identify whether inactivation of FOXO1 induced neoplastic follicular-helper T (Tfh) cell polarization and function.ResultsPatients with low FOXO1 protein levels were prone to have an advanced tumor stage (P = 0.049), higher ECOG ps (P = 0.024), the presence of bone marrow invasion (P = 0.000), and higher IPI (P = 0.035). Additionally, the survival rates of patients in the FOXO1 high-expression group were significantly better than those in the FOXO1 low-expression group (χ2 = 5.346, P = 0.021). We also observed that inactivation of FOXO1 increased CD4+ T cell proliferation and altered the survival and cell-cycle progression of CD4+ T cells. Finally, we confirmed that inactivation of FOXO1 induces Tfh cell programing and function.ConclusionsInactivation of FOXO1 in AITL plays a key role in the tumorigenesis and progression of AITL. We propose that FOXO1 expression could be a useful prognostic marker in AITL patients to predict poor survival, and to design appropriate therapeutic strategies. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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