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J Immunother. 2018 Sep;41(7):319-328. doi: 10.1097/CJI.0000000000000234.

Effects of Glycogen Synthase Kinase-3β Inhibitor TWS119 on Proliferation and Cytokine Production of TILs From Human Lung Cancer.

Author information

1
Key Laboratory of Tropical Disease Control of Sun Yat-Sen University, Ministry of Education, The Institute of Immunology of Zhong Shan Medical School.
2
Department of Basic Medicine, Xiangnan University, Chenzhou, Hunan.
3
The third people's Hospital of Hainan Province, Sanya, Hainan, China.
4
Zhong Shan Medical School, Sun Yat-Sen University.
5
The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.

Abstract

The canonical Wnt-β-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-3β 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-γ production were detected. Our data showed that TWS119 does not affect the production of IFN-γ in TILs compared with the control group; whereas TWS119 inhibited IFN-γ 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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