CELL INTELLIGENCE · 肿瘤细胞治疗研究

UNLABELLED: Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative therapy for patients diagnosed with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). γδ+ T-cells, a rare subpopulation of T-cells with both innate and adaptive anticancer functions, have been understudied and the role of different γδ+ T-cell subsets after HSCT is unclear. OBJECTIVES: We aimed to characterise the γδ+ T-cells reconstitution post-HSCT, investigating their association with graft-versus-host disease (GvHD) treatment and occurrence, and cytomegalovirus (CMV) reactivation. METHODS: Peripheral blood samples from AML and MDS patients and their respective donors were immunophenotyped by flow cytometry before and at several time points after HSCT. Additionally, next-generation sequencing of the TRG locus was performed to assess clonal dynamics and repertoire diversity. RESULTS: Early after HSCT, γδ+ T-cells showed a similar phenotype compared to pre-HSCT, and stable repertoires were observed up to 6 months post-HSCT. Patients with acute GVHD presented a higher frequency of CD8 in γδ+ T-cells, and γδ+ T-cell and subsets frequencies were not affected by anti-thymocyte globulin prophylaxis. Donor-derived Vδ2+ T-cell central memory phenotype was associated with a reduced risk of CMV reactivation in the recipient and with repertoire disturbance. Effector memory cells displaying a specific HLA-DR+ CD86+ phenotype were associated with CMV reactivation and a higher proportion of hyperexpanded clonotypes prior to transplantation. CONCLUSION: Overall, Vδ1+ and Vδ2+ T-cell phenotypic profiles and γδ TCR repertoire remain stable post-HSCT. This stability is disrupted by CMV reactivation, which is potentially associated with γδ+ T-cells of donor origin and γδ TCR repertoire.