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Updated: Sep 8, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Glycogen Synthase Kinase-3 (GSK-3) Regulation of Inhibitory Coreceptor Expression in T-cell Immunity
Mark E Issa1,2, Christopher E Rudd1,2
1Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Abstract:
The serine/threonine kinase, glycogen synthase kinase 3 (GSK-3) has been implicated in immune cell activation and function. Our recent studies have shown that the abrogation of GSK-3 activity down-regulates the expression of key inhibitory receptors PD-1 and LAG-3. It also regulates the expression of the transcription factor NFAT which, in turn, is responsible for inhibiting PD-1/LAG-3 transcription as well as activating the expression of cytolytic effector proteins such as perforin and granzyme B. The role of components of the Wnt signaling pathway in these events remains to be fully uncovered. This mini-review discusses the recent discoveries that have elucidated the role of the GSK-3 signaling pathway in cancer immunotherapy.
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