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@ARTICLE{Mathioudaki:294790,
author = {A. Mathioudaki$^*$ and X. Wang and D. Sedloev and R. Huth
and A. Kamal and M. Hundemer and Y. Liu and S. Vasileiou and
P. Lulla and C. Müller-Tidow and P. Dreger and T. Luft and
T. Sauer and M. Schmitt and J. B. Zaugg and C. Pabst},
title = {{T}he remission status of {AML} patients after allo-{HCT}
is associated with a distinct single-cell bone marrow
{T}-cell signature},
journal = {Blood},
volume = {143},
number = {13},
issn = {0006-4971},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2024-02502},
pages = {1269 - 1281},
year = {2024},
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.},
cin = {B450},
ddc = {610},
cid = {I:(DE-He78)B450-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
doi = {10.1182/blood.2023021815},
url = {https://inrepo02.dkfz.de/record/294790},
}