Single-cell analysis reveals cytotoxic and memory CD8⁺ T cells associated with prolonged survival in relapsed/refractory leukaemia patients after haplo+cord haematopoietic stem cell transplantation

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.

Keywords

CD8⁺ T cells / haplo+cord HSCT / relapsed/refractory leukaemia / single cord HSCT / single-cell multi-omics

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