Acquisition of an immunosuppressive microenvironment after anti-CD19 CAR T-cell therapy is associated with T-cell dysfunction and resistance.

ABSTRACT:

Background

Chimeric antigen receptor (CAR) T cells targeting CD19 induce durable responses in B-cell acute lymphoblastic leukemia (B-ALL). However, the contribution of the tumor microenvironment to the therapeutic response after CAR T-cell treatment remains incompletely understood.

Methods

We performed single-cell RNA sequencing and spectral flow cytometry-based analyses of bone marrow-resident immune cells from B-ALL patients before and after CAR T-cell treatment.

Results

We observed profound changes in the microenvironment in response to CAR T-cell-mediated inflammation, including an increase in myeloid cells. Significant induction of the interferon response, hypoxia, and TGF-β signaling was accompanied by expansion of myeloid-derived suppressor cells (MDSCs) and en

SUBMITTER: Ponzo M 

PROVIDER: S-EPMC12557794 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature