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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 regul