Inhibiting Akt1 and Akt2 but not Akt3 in a subject has been found to be an effective immune therapy that delays the exhaustion of CD8 T cells, prolongs CD8 T cell survival, preserves a remarkably high percentage of TCM cells, and significantly increases TCM proliferative potential upon reencountering antigen. In a preferred embodiment, the Akt1 and Akt2 inhibitors do not inhibit Akt3. Preferred small molecule inhibitors include, but are not limited to MK-2206, AZD5363, (1,3-Dihydro-1-(1-((4-(6-phenyl-1H-imidazo[4,5-g]quinoxalin-7-yl)phenyl)methyl)-4-piperidinyl)-2H-benzimidazol-2-one trifluoroacetate salt hydrate or combinations thereof.
