Allogeneic haematopoietic stem-cell transplantation (AHST) is the only curative treatment for many patients with blood cancer. Donor-derived immune-cells are critical for protection against viral infection after AHST and provide graft-versus-tumour (GvT) effects to prevent cancer relapse. However, a proportion of alloreactive donor T-cells can recognize and damage healthy patient tissues resulting in acute graft-versus-host disease (aGvHD), a major barrier to successful AHST. We use novel mass cytometry technology following AHST in patients, to define the global landscape of immune-cell populations preceding development of aGvHD and to identify a dominant immunoregulatory role for subsets of CD56hi NK cells in limiting alloreative T-cell expansion and aGvHD, hence providing evidence that immunoregulatory NK cell(NKreg) represent a new therapeutic opportunity to prevent aGvHD after AHST.

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