Using a coculture of stromal cells expressing the notch ligand, Kondo et al. converted activated CD4+ and CD8+ T cells into a memory-like state, characterized by lack of surface PD-1 and CTLA-4, increased expression of Bcl 2, strong anti-tumor activity, and a high proliferative and survival potential in vivo, possibly due to reduced expression of the cell cycle regulator p53.
Adoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8+ TSCM cells can be generated in vitro from naive CD8+ T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM-like cells in vitro (iTSCM cells) from activated CD4+ and CD8+ T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iTSCM cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.