Single-Cell Multi-Omics Reveals Immune Characteristics of T Cells in Patients with Relapsed/Refractory Leukemia after Haplo+Cord HSCT

Single-cell multi-omics reveals immune characteristics of T cells in patients with relapsed/refractory leukemia after haplo+cord HSCT

Background:

The treatment of relapsed/refractory leukaemia (R/R) is a significant challenge in medical oncology. Allogeneic haematopoietic stem cell transplantation has been demonstrated as the only cure method ; however, long-term survival rates for patients with R/R leukaemia remain low. Our current study's findings indicate that sequential transplantation of haploidentical stem cell and umbilical cord blood (haplo+cord HSCT) may result in enhanced survival outcomes for patients with R/R leukemia. Nevertheless, the underlying mechanisms remain largely unexplored.

Methods:

A comparative analysis of single-cell gene expression and chromatin accessibility was conducted in bone marrow samples from 16 patients who had undergone haplo+cord or single cord HSCT. Furthermore, flow cytometry was conducted to substantiate our findings.

Results:

Distinct compositions and functions of global immune landscapes were observed, with haplo+cord HSCT exhibiting effective anti-tumour and anti-viral immunity, mediated by type I interferon signalling. The analysis of T cells revealed the presence of a group of CD8+ T cells expressing GNLY and CX3CR1, which were observed to be enriched in recipients of haplo+cord HSCT. This finding was subsequently confirmed by flow cytometry. It is noteworthy that gene signature scoring indicates that haplo+cord-enriched CD8⁺ T cells possess a dual effector and memory property, which may provide long-term protection. Ultimately, an integrated single-cell multi-omics analysis elucidated the regulatory networks governing lineage-specific gene expression following transplantation. To illustrate, the expression of GNLY in CD8⁺ T cells enriched in haplo+cord transplants was found to be regulated by an enhancer network situated within a CTCF-mediated chromatin loop.

Conclusions: The collective findings of the single-cell multi-omics analyses demonstrate that CX3CR1⁺GNLY⁺ CD8+ T cells, which exhibit effector and memory properties, contributed to the enhanced survival of patients with R/R leukaemia who underwent haplo+cord HSCT.

No relevant conflicts of interest to declare.