Abstract | Objective: Angioimmunoblastic 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. Methods: FOXO1 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. Results: Patients 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. Conclusions: Inactivation 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.
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Authors | Meifang Xu, Fei Wang, Hong Chen, Lin Liu, Wenwen Liu, Yinghong Yang, Qiaoling Zheng, Lihong Zhang, Xiaoxuan Li, Suxia Lin, Shengbing Zang |
Journal | Cancer biology & medicine
(Cancer Biol Med)
Vol. 16
Issue 4
Pg. 743-755
(11 2019)
ISSN: 2095-3941 [Print] China |
PMID | 31908892
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2019 Cancer Biology & Medicine. |