P427: THE SINGLE CELL T CELL LANDSCAPE OF AML PATIENTS POST ALLOGENEIC STEM CELL TRANSPLANTATION

作者：A. Mathioudaki, Xingjin Wang, R. Huth, J. Zaugg, C. Pabst · 发表于：HemaSphere · 年份：2022 · DOI：10.1097/01.hs9.0000844596.47578.04 · 研究领域：Acute Myeloid Leukemia Research、CAR-T cell therapy research

Background: In Acute myeloid leukemia (AML), chemotherapy may lead to long-term remission, but allogeneic stem cell transplantation (alloSCT) often remains the only curative therapeutic approach, particularly in AML with high-risk genetics. However, not every patient responds to alloSCT. Several hypotheses have been associated with therapy failure, such as the incapability of T cells to recognize and eliminate residual leukemia stem cells (LSCs), which thus escape the graft-versus-leukemia (GVL) effect. However, the role of the T cells’ repertoire in therapy outcome still remains unclear. Aims: Here, we investigated the impact of the bone marrow (BM) T cell composition on the therapy outcome of AML patients after alloSCT. Methods: We performed single-cell RNA sequencing (scRNA-seq) of T cells and hematopoietic stem and progenitor cells (HSPCs) isolated from BM aspirates 100 days post alloSCT of three patients in complete remission (CR) versus three suffering relapse (REL). We investigated the prognostic impact of putative T-cell biomarkers in therapy outcome, using flow cytometry analysis on an independent cohort. Results: Using scRNA-seq, we identified 21 T cell and 9 HSPC populations and observed differences in T cell population abundances between REL and CR. In particular, we observed an enrichment of specific CD8+ T cell subsets in the CR group, while certain CD4+ T cell subsets, such as regulatory T cells were enriched in REL patients. Furthermore, we observed an increas...