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000294790 0247_ $$2doi$$a10.1182/blood.2023021815
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000294790 1001_ $$0P:(DE-He78)fc0c97c9d01deff15d0a1f0cb8402459$$aMathioudaki, Anna$$b0$$udkfz
000294790 245__ $$aThe remission status of AML patients after allo-HCT is associated with a distinct single-cell bone marrow T-cell signature
000294790 260__ $$aWashington, DC$$bAmerican Society of Hematology$$c2024
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000294790 520__ $$aAcute myeloid leukemia (AML) is a hematologic malignancy for which allogeneic hematopoietic cell transplantation (allo-HCT) often remains the only curative therapeutic approach. However, incapability of T cells to recognize and eliminate residual leukemia stem cells might lead to an insufficient graft-versus-leukemia (GVL) effect and relapse. Here, we performed single-cell RNA-sequencing (scRNA-seq) on bone marrow (BM) T lymphocytes and CD34+ cells of 6 patients with AML 100 days after allo-HCT to identify T-cell signatures associated with either imminent relapse (REL) or durable complete remission (CR). We observed a higher frequency of cytotoxic CD8+ effector and gamma delta (γδ) T cells in CR vs REL samples. Pseudotime and gene regulatory network analyses revealed that CR CD8+ T cells were more advanced in maturation and had a stronger cytotoxicity signature, whereas REL samples were characterized by inflammatory tumor necrosis factor/NF-κB signaling and an immunosuppressive milieu. We identified ADGRG1/GPR56 as a surface marker enriched in CR CD8+ T cells and confirmed in a CD33-directed chimeric antigen receptor T cell/AML coculture model that GPR56 becomes upregulated on T cells upon antigen encounter and elimination of AML cells. We show that GPR56 continuously increases at the protein level on CD8+ T cells after allo-HCT and confirm faster interferon gamma (IFN-γ) secretion upon re-exposure to matched, but not unmatched, recipient AML cells in the GPR56+ vs GPR56- CD8+ T-cell fraction. Together, our data provide a single-cell reference map of BM-derived T cells after allo-HCT and propose GPR56 expression dynamics as a surrogate for antigen encounter after allo-HCT.
000294790 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0
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000294790 7001_ $$aWang, Xizhe$$b1
000294790 7001_ $$aSedloev, David$$b2
000294790 7001_ $$aHuth, Richard$$b3
000294790 7001_ $$aKamal, Aryan$$b4
000294790 7001_ $$aHundemer, Michael$$b5
000294790 7001_ $$aLiu, Yi$$b6
000294790 7001_ $$aVasileiou, Spyridoula$$b7
000294790 7001_ $$00000-0002-7707-2331$$aLulla, Premal$$b8
000294790 7001_ $$aMüller-Tidow, Carsten$$b9
000294790 7001_ $$aDreger, Peter$$b10
000294790 7001_ $$aLuft, Thomas$$b11
000294790 7001_ $$aSauer, Tim$$b12
000294790 7001_ $$aSchmitt, Michael$$b13
000294790 7001_ $$00000-0001-8324-4040$$aZaugg, Judith B.$$b14
000294790 7001_ $$aPabst, Caroline$$b15
000294790 773__ $$0PERI:(DE-600)1468538-3$$a10.1182/blood.2023021815$$gVol. 143, no. 13, p. 1269 - 1281$$n13$$p1269 - 1281$$tBlood$$v143$$x0006-4971$$y2024
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