A central step in T-cell immunotherapy is the expansion of a starting population into therapeutically potent numbers of these "living drugs". This process can be enhanced by replacing the mechanically stiff materials used for activation with softer counterparts. However, this mechanosensitive expansion response varies between individuals, impeding the full deployment of potential cell immunotherapy. This report identifies the sources of this variability, ultimately improving the reliability of T-cell expansion. T cells from a cohort of healthy donors were phenotypically characterized, activated, and expanded in vitro on soft and hard substrates, capturing and quantifying a wide range of mechanosensing responses. An analysis of expansion against demographic and phenotypic features correlated mechanosensing with the percentage of effector T cells (T