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Title: The role of stem cell graft derived natural killer cells in regulating patient outcomes from allogeneic haematopoietic stem cell transplantation
Author: Maggs, Luke
ISNI:       0000 0004 7432 485X
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2018
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Myeloid and lymphoid malignancies are potentially curable through a graft versus leukaemia (GvL) effect following allogeneic haematopoietic stem cell transplantation. Whilst donor T cell are thought to be the main mediators of GvL, the effect of donor NK cells within HLA matched T cell depleted transplant setting is more unclear. Patient blood samples were analysed during the first month post-transplant, with higher reconstitution of NK cells at two weeks conferring a relapse protection association. Donor stem cell graft samples, from which NK cells within the patient at two weeks are thought to be derived, similarly displayed a strong association between high NK cell dose and protection from disease relapse. CD56dimDNAM+ NK cells were found to be the population with the most significant association. The ability of NK cells to kill AML blasts in a DNAM dependent manner was shown indicating that direct killing of residual tumour cells may be a valid mechanism of GvL. These findings suggest that optimising the number of NK cells within stem cell grafts should be considered as a means to prevent disease relapse.
Supervisor: Not available Sponsor: Medical Research Council (MRC) ; Bloodwise
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR Microbiology ; QR180 Immunology ; RB Pathology ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)