AML induces TTCR-C4 NK-like transcriptional skewing associated with low persistence and dysfunction

This dataset includes single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data generated to investigate T cell responses in the context of acute myeloid leukemia (AML) and WT1-specific TCR-T cell therapy. The scRNA-seq dataset comprises peripheral blood (PB) and bone marrow (BM) samples from AML patients treated with WT1-specific TCR-engineered T cells (TCR-T). We specifically profiled both endogenous CD8⁺ T cells and TCR-T cells to characterize their transcriptional states and assess the impact of AML on T cell differentiation and function. In-depth analysis of samples from a patient with a durable clinical response provided insights into the transcriptional profiles of TCR-T cells over time, including after Azacitidine treatment. The bulk RNA-seq dataset was generated using an in vitro model of AML-induced T cell dysfunction. CD8⁺ transgenic WT1-specific T cells (TTCR37-45) recognizing the HLA-A0201-restricted WT137-45 epitope were repeatedly challenged with WT1-expressing HLA-A0201-transduced K562 AML cells. Loss of tumor control by day 13 was associated with a transition from a naïve/stem-like transcriptional state to one enriched in effector, activation/exhaustion, and NK-like/Temra gene signatures. By day 23, activation/exhaustion markers declined while NK-like/Temra-associated genes persisted or increased, highlighting a phenotypic shift in dysfunctional T cells.