Abstract Backgroud Allogeneic haematopoietic stem cell transplantation (allo‐HSCT) is a curative treatment for haematological malignancies. Sequential transplantation of haploidentical stem cell and umbilical cord blood (haplo+cord HSCT) among recipients with relapsed/refractory (R/R) leukaemia exhibited superior survival outcomes compared with single cord HSCT. However, the underlying mechanisms remain unclear. Methods Here, we profiled and compared single‐cell gene expression and chromatin accessibility in bone marrow from 16 patients receiving haplo+cord or single cord HSCT. Results We observed distinct compositions and functions of global immune landscapes, with haplo+cord HSCT exhibiting effective anti‐tumour and anti‐viral immunity mediated by type I interferon signalling. Analysis of T cells revealed specific CD8 + T cell subtype (CD8‐c1), enriched in recipients with haplo+cord HSCT, which was also confirmed by flow cytometry. Functionally, gene signature scoring suggests a dual effector and memory property of CD8‐c1 that potentially offers long‐term protection. Furthermore, single‐cell multi‐omics analysis delineated the expression of cytotoxic‐related genes up‐regulated in CD8‐c1 are cooperatively regulated by enhancer networks. Notably, a proportion‐based survival analysis indicated that high proportion of CD8‐c1 was associated with better survival. Conclusion Our results collectively demonstrate that a population of CD8 + T cells with effector and memory properties contributes to improved survival in patients with R/R leukaemia receiving haplo+cord HSCT.
Li et al. (Sun,) studied this question.