Inactivation of GSK-3 either through SMIs or by using GSK-3α/β siRNA led to a reduction in PD-1 expression and in both cases reduced B16 pulmonary metastasis to a similar extent as seen in Pdcd1-/- mice. In each model, GSK-3 SMIs inhibited Pdcd1 transcription and PD-1 expression on tumor infiltrating T-cells (TILs), while increasing Tbx21 (T-bet) transcription30 and the presence of CD8+ TILs expressing CD107a (LAMP1), granzyme B (GZMB) and IFNγ 131. The gene discussed is GZMB; the disease is neoplasm.