Addition of DMSO to T cell cultures skews differentiation towards a memory phenotype.

Dimethyl sulfoxide (DMSO) is a polar aprotic organic solvent that is widely used in biological applications. It is routinely applied as a cryoprotectant for long-term cell freezing as well as to dissolve peptides or drugs for immune cell functional assays. We report on a remarkable impact of low concentrations of DMSO on in vitro expansion of the total CD3+ pool isolated from human PBMCs as well as on the purified CD8+ T cell fraction thereof in the presence of different cytokine combinations typically used for therapeutic T cell expansion. Characterizing survival, proliferation, activation, exhaustion and differentiation, we demonstrate that DMSO at low concentrations substantially skews the differentiation of T cells towards a memory phenotype in a dose-dependent way. This is a desirable outcome for the field of adoptive T cell therapies for cancer, where it has been established that T cells with a memory phenotype exert superior anti-cancer immune responses.