This disclosure relates to compositions and methods of reversing senescence in T cells by interrupting vasoactive intestinal peptide (VIP) signalling and/or inhibiting phosphatidylinositol- 3 -kinase (PI3 kinase) inhibitor signalling and uses in managing cancer and chronic viral infections. In certain embodiments, the disclosure contemplates methods of reversing T cell senescence by mixing T cell in vitro with an agent that prevents VIP from interacting with VIP receptors and/or a PI3 Kinase inhibitor. In certain embodiments, the disclosure contemplates the expansion of senescent T cells by mixing with a PI3 kinase inhibitor, an agent that block VIP and VIP receptor signalling, a VIP degrading enzyme, and combinations thereof.
