TY  - JOUR
AU  - Mathioudaki, Anna
AU  - Wang, Xizhe
AU  - Sedloev, David
AU  - Huth, Richard
AU  - Kamal, Aryan
AU  - Hundemer, Michael
AU  - Liu, Yi
AU  - Vasileiou, Spyridoula
AU  - Lulla, Premal
AU  - Müller-Tidow, Carsten
AU  - Dreger, Peter
AU  - Luft, Thomas
AU  - Sauer, Tim
AU  - Schmitt, Michael
AU  - Zaugg, Judith B.
AU  - Pabst, Caroline
TI  - The remission status of AML patients after allo-HCT is associated with a distinct single-cell bone marrow T-cell signature
JO  - Blood
VL  - 143
IS  - 13
SN  - 0006-4971
CY  - Washington, DC
PB  - American Society of Hematology
M1  - DKFZ-2024-02502
SP  - 1269 - 1281
PY  - 2024
AB  - 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. 
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1182/blood.2023021815
UR  - https://inrepo02.dkfz.de/record/294790
ER  -