Effects of Glycogen Synthase Kinase-3[beta] Inhibitor TWS119 on Proliferation and Cytokine Production of TILs From Human Lung Cancer.
Tang, Ying Ying *; Sheng, Si Yuan +; Lu, Chuan Gang ++; Zhang, Yu Qing [S]; Zou, Jian Yong [//]; Lei, Yi Yan [//]; Gu, Yong [//]; Hong, Hai *
Journal of Immunotherapy.
41(7):319-328, September 2018.
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The canonical Wnt-[beta]-catenin signaling pathway arrests the differentiation of T cells and plays an important role in phenotypic maintenance of naive T cells and stem cell-like memory T cells in human peripheral blood, but its effect on tumor-infiltrating lymphocytes (TILs) from non-small cell lung cancer is little known. In this study, we showed that glycogen synthase kinase-3[beta] inhibitor TWS119 has different effects on CD4 and CD8 T cells in TILs. TWS119 preserved the expansion of naive T cell and CD8 stem cell-like memory T cells, and induced CD8 effector T-cell proliferation in TILs. To further determine whether TWS119 impaired the effector function of TILs, TILs were stimulated with polyclonal stimulation, IL-2 and IFN-[gamma] production were detected. Our data showed that TWS119 does not affect the production of IFN-[gamma] in TILs compared with the control group; whereas TWS119 inhibited IFN-[gamma] secretion of T cells from healthy donor. IL-2 production in CD4 central memory T cells and CD4 effector memory T cells from TILs was significantly increased with the TWS119 treatment; TWS119 also promoted the secretion of IL-2 in all cell subsets of CD8 TILs. These findings reveal that TWS119 has a distinct effect on the proliferation and cytokine production of TILs, and provide new insights into the clinical application of TILs with TWS119 treatment for the adoptive immunotherapy.
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