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.
摘要:
为了符合“表单遵循函数\”的规则,细胞的形态方面可以反映其作用。这里,表明淋巴细胞的细胞粒度,由其固有侧向散射(SSC)表示,是其细胞状态和功能的有效指标。淋巴细胞的粒度从初始到终末效应物状态增加。高通量细胞分选产生可以介导即时效应功能的SSChigh群体,和高度多产的SSClow种群,可以引起内存池的补充。来自年轻SSClow群体的CAR-T细胞具有理想的免疫治疗属性,表现为原始样细胞和干细胞记忆(TSCM)样细胞的增加以及平衡的CD4/CD8比率,以及增强的体外和体内靶向杀伤。总之,基于生物物理特性的淋巴细胞分离是一种有效的无标记选择细胞的方法,这些细胞具有共同的功能,并且可以在基于细胞的免疫疗法中具有重要的应用。