Functional diversification and dynamics of CAR-T cells in patients with B-ALL

Cell Rep. 2023 Oct 31;42(10):113263. doi: 10.1016/j.celrep.2023.113263. Epub 2023 Oct 17.


Understanding of cellular evolution and molecular programs of chimeric antigen receptor-engineered (CAR)-T cells post-infusion is pivotal for developing better treatment strategies. Here, we construct a longitudinal high-precision single-cell transcriptomic landscape of 7,578 CAR-T cells from 26 patients with B cell acute lymphoblastic leukemia (B-ALL) post-infusion. We molecularly identify eight CAR-T cell subtypes, including three cytotoxic subtypes with distinct kinetics and three dual-identity subtypes with non-T cell characteristics. Remarkably, long-term remission is coincident with the dominance of cytotoxic subtypes, while leukemia progression is correlated with the emergence of subtypes with B cell transcriptional profiles, which have dysfunctional features and might predict relapse. We further validate in vitro that the generation of B-featured CAR-T cells is induced by excessive tumor antigen stimulation or suppressed TCR signaling, while it is relieved by exogenous IL-12. Moreover, we define transcriptional hallmarks of CAR-T cell subtypes and reveal their molecular changes along computationally inferred cellular evolution in vivo. Collectively, these results decipher functional diversification and dynamics of peripheral CAR-T cells post-infusion.

Keywords: B cell acute lymphoblastic leukemia; CAR-T cell; CP: Cancer; CP: Cell biology; adoptive immunotherapy; cellular evolution; dynamic features; longitudinal study; single-cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD19
  • Humans
  • Immunotherapy, Adoptive / methods
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma*
  • Receptors, Chimeric Antigen* / genetics
  • T-Lymphocytes


  • Antigens, CD19
  • Receptors, Chimeric Antigen