The remission status of AML patients after allo-HCT is associated with a distinct single-cell bone marrow T-cell signature

• Verfasst von: Mathioudaki, Anna [VerfasserIn]
• Verfasst von: Wang, Xizhe [VerfasserIn]
• Verfasst von: Sedloev, David [VerfasserIn]
• Verfasst von: Huth, Richard [VerfasserIn]
• Verfasst von: Kamal, Aryan [VerfasserIn]
• Verfasst von: Hundemer, Michael [VerfasserIn]
• Verfasst von: Liu, Yi [VerfasserIn]
• Verfasst von: Vasileiou, Spyridoula [VerfasserIn]
• Verfasst von: Lulla, Premal [VerfasserIn]
• Verfasst von: Müller-Tidow, Carsten [VerfasserIn]
• Verfasst von: Dreger, Peter [VerfasserIn]
• Verfasst von: Luft, Thomas [VerfasserIn]
• Verfasst von: Sauer, Tim [VerfasserIn]
• Verfasst von: Schmitt, Michael [VerfasserIn]
• Verfasst von: Zaugg, Judith B. [VerfasserIn]
• Verfasst von: Pabst, Caroline [VerfasserIn]
• Titel: The remission status of AML patients after allo-HCT is associated with a distinct single-cell bone marrow T-cell signature
• Verf.angabe: Anna Mathioudaki, Xizhe Wang, David Sedloev, Richard Huth, Aryan Kamal, Michael Hundemer, Yi Liu, Spyridoula Vasileiou, Premal Lulla, Carsten Müller-Tidow, Peter Dreger, Thomas Luft, Tim Sauer, Michael Schmitt, Judith B. Zaugg, and Caroline Pabst
• E-Jahr: 2024
• Jahr: March 28 2024
• Umfang: 13 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 15.11.2024
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 2024
• Band/Heft Quelle: 143(2024), 13 vom: März, Seite 1269-1281
• ISSN Quelle: 1528-0020
• DOI: doi:10.1182/blood.2023021815
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1908735740

Abstract

Acute myeloid leukemia (AML) is a hematologic malignancy for which allogeneic hematopoietic cell transplantation (allo-HCT) often remains the only curative therapeutic approach. However, incapability of T cells to recognize and eliminate residual leukemia stem cells might lead to an insufficient graft-versus-leukemia (GVL) effect and relapse. Here, we performed single-cell RNA-sequencing (scRNA-seq) on bone marrow (BM) T lymphocytes and CD34+ cells of 6 patients with AML 100 days after allo-HCT to identify T-cell signatures associated with either imminent relapse (REL) or durable complete remission (CR). We observed a higher frequency of cytotoxic CD8+ effector and gamma delta (γδ) T cells in CR vs REL samples. Pseudotime and gene regulatory network analyses revealed that CR CD8+ T cells were more advanced in maturation and had a stronger cytotoxicity signature, whereas REL samples were characterized by inflammatory tumor necrosis factor/NF-κB signaling and an immunosuppressive milieu. We identified ADGRG1/GPR56 as a surface marker enriched in CR CD8+ T cells and confirmed in a CD33-directed chimeric antigen receptor T cell/AML coculture model that GPR56 becomes upregulated on T cells upon antigen encounter and elimination of AML cells. We show that GPR56 continuously increases at the protein level on CD8+ T cells after allo-HCT and confirm faster interferon gamma (IFN-γ) secretion upon re-exposure to matched, but not unmatched, recipient AML cells in the GPR56+ vs GPR56- CD8+ T-cell fraction. Together, our data provide a single-cell reference map of BM-derived T cells after allo-HCT and propose GPR56 expression dynamics as a surrogate for antigen encounter after allo-HCT.