Non-redundant activity of GSK-3α and GSK-3β in T cell-mediated tumor rejection

iScience

卷:24

Gary Shaw¹  Alison Taylor²  Kenneth A. Maclennan³  Graham P. Cook³  Christopher E. Rudd³  Lynette Steele³  Aarren J. Mannion³ 

[1] Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden;

[2] Division of Immunology-Oncology Research Center, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada;

[3] Leeds Institute of Medical Research, University of Leeds, School of Medicine, Wellcome Trust Brenner Building, St James's University Hospital, Leeds LS9 7TF, UK;

关键词: cancer;    cell biology;    functional aspects of cell biology;    immunology;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Glycogen synthase kinase-3 (GSK-3) is a positive regulator of PD-1 expression in CD8+ T cells and GSK-3 inhibition enhances T cell function and is effective in the control of tumor growth. GSK-3 has two co-expressed isoforms, GSK-3α and GSK-3β. Using conditional gene targeting, we demonstrate that both isoforms contribute to T cell function to different degrees. Gsk3b−/− mice suppressed tumor growth to the same degree as Gsk3a/b−/− mice, whereas Gsk3a−/− mice behaved similarly to wild-type, revealing an important role for GSK-3β in regulating T cell-mediated anti-tumor immunity. The individual GSK-3α and β isoforms have differential effects on PD-1, IFNγ, and granzyme B expression and operate in synergy to control PD-1 expression and the infiltration of tumors with CD4 and CD8 T cells. Our data reveal a complex interplay of the GSK-3 isoforms in the control of tumor immunity and highlight non-redundant activity of GSK-3 isoforms in T cells, with implications for immunotherapy.

【 授权许可】

Unknown