Fate induction in CD8 CAR T cells through asymmetric cell division.

ABSTRACT: Early expansion and long-term persistence predict efficacy of chimeric antigen receptor T cells (CARTs)^1-7, but mechanisms governing effector versus memory CART differentiation and whether asymmetric cell division induces differential fates in human CARTs remain unclear. Here we show that target-induced proximity labelling enables isolation of first-division proximal-daughter and distal-daughter CD8 CARTs that asymmetrically distribute their surface proteome and transcriptome, resulting in divergent fates. Target-engaged CARs remain on proximal daughters, which inherit a surface proteome resembling activated-undivided CARTs, whereas the endogenous T cell receptor and CD8 enrich on distal daughters, whose surface proteome resembles resting CARTs, correlating with glycolytic and o

SUBMITTER: Lee CS 

PROVIDER: S-EPMC11410665 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature