Cell Granularity Reflects Immune Cell Function and Enables Selection of Lymphocytes with Superior Attributes for Immunotherapy

作者：Tongjin Wu, Joel Heng Loong Tan, Wei‐Xiang Sin, Yen Hoon Luah, Sue Yee Tan, Myra Goh, Michael E. Birnbaum, Qingfeng Chen, Lih Feng Cheow · 发表于：Advanced Science · 年份：2023 · DOI：10.1002/advs.202302175 · 被引用次数：25 · 研究领域：CAR-T cell therapy research、T-cell and B-cell Immunology、Immune Cell Function and Interaction

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 SSC high population that can mediate immediate effector functions, and a highly prolific SSC low population that can give rise to the replenishment of the memory pool. CAR‐T cells derived from the younger SSC low population possess desirable attributes for immunotherapy, manifested by increased naïve‐like cells and stem cell memory (T SCM )‐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.