Two-stage CD8⁺ CAR T-cell differentiation in patients with large B-cell lymphoma.

ABSTRACT: Advancements in chimeric antigen receptor (CAR) T-cell therapy for treating diffuse large B-cell lymphoma (DLBCL) have been limited by an incomplete understanding of CAR T-cell differentiation in patients. Here, we show via single-cell, multi-modal, and longitudinal analyses, that CD8⁺ CAR T cells from DLBCL patients successfully treated with axicabtagene ciloleucel undergo two distinct waves of clonal expansion in vivo. The first wave is dominated by an exhausted-like effector memory phenotype during peak expansion (day 8-14). The second wave is dominated by a terminal effector phenotype during the post-peak persistence period (day 21-28). Importantly, the two waves have distinct ontogeny from the infusion product and are biologically uncoupled. Precursors of the first wave exh

SUBMITTER: Cao G 

PROVIDER: S-EPMC12055983 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature