{Reference Type}: Journal Article
{Title}: Cell Granularity Reflects Immune Cell Function and Enables Selection of Lymphocytes with Superior Attributes for Immunotherapy.
{Author}: Wu T;Tan JHL;Sin WX;Luah YH;Tan SY;Goh M;Birnbaum ME;Chen Q;Cheow LF;
{Journal}: Adv Sci (Weinh)
{Volume}: 10
{Issue}: 28
{Year}: 2023 10 6
{Factor}: 17.521
{DOI}: 10.1002/advs.202302175
{Abstract}: In keeping with the rule of "form follows function", morphological aspects of a cell can reflect its role. Here, it is shown that the cellular granularity of a lymphocyte, represented by its intrinsic side scatter (SSC), is a potent indicator of its cell state and function. The granularity of a lymphocyte increases from naïve to terminal effector state. High-throughput cell-sorting yields a SSChigh population that can mediate immediate effector functions, and a highly prolific SSClow population that can give rise to the replenishment of the memory pool. CAR-T cells derived from the younger SSClow population possess desirable attributes for immunotherapy, manifested by increased naïve-like cells and stem cell memory (TSCM )-like cells together with a balanced CD4/CD8 ratio, as well as enhanced target-killing in vitro and in vivo. Altogether, lymphocyte segregation based on biophysical properties is an effective approach for label-free selection of cells that share collective functions and can have important applications for cell-based immunotherapies.