Single-cell RNA sequencing of human double-negative T cells reveals a favorable cellular signature for cancer therapy.

ABSTRACT:

Background

Allogeneic double-negative T-cell (DNT) therapy has emerged as a novel, off-the-shelf cellular treatment with clinical feasibility, safety, and promising efficacy against leukemia. However, the biology of DNTs is less well characterized, and how DNT therapy distinguishes from conventional γδ T-cell therapy remains unclear. Collectively, this hinders our ability to bolster DNT functionalities in cancer therapy. Here, we performed single-cell RNA sequencing with in vitro and in vivo functional analysis on DNTs. As a significant proportion of DNTs express Vγ9Vδ2 (Vδ2) TCR chain, we compared DNTs with donor-matched conventional Vδ2 T cells expanded with zoledronic acid.

Methods

Healthy donor-derived allogeneic DNTs and Vδ2 T cells were expanded ex vivo. Single-cell RN

SUBMITTER: Tin E 

PROVIDER: S-EPMC12007110 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature