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Review
. 2017 Jun 7:8:496.
doi: 10.3389/fimmu.2017.00496. eCollection 2017.

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

Anne M Dickinson  1 , Jean Norden  1 , Shuang Li  2 , Ilona Hromadnikova  2 , Christoph Schmid  3 , Helga Schmetzer  4 , Hans Jochem-Kolb  5
Affiliations
Review

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

Anne M Dickinson et al. Front Immunol. .

Abstract

The success of hematopoietic stem cell transplantation (HSCT) lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL), caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter.

Keywords: LAA specific T cells; allogenic natural killer cells; animal models; donor lymphocyte infusion; graft-versus-leukemia effect; invariant natural killer T cells (i)NKT; leukaemia associated antigens (LAA); leukaemia derived dendritic cells; leukaemia specific antigens.

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Figures

Figure 1
Figure 1
Donor-versus-recipient natural killer (NK) alloreactivity. NK cell function is regulated by KIR interactions with matched HLA class I alleles. If HLA is mismatched in transplant recipient leukemic cells, NK cells are relieved from inhibition and induce cell lysis. In the case for inhibitor KIRs, binding with matching HLA prevents donor NK cell activation to self. For activating KIRs, donor NK cells that bind the matched HLA are activated and induce cell lysis of transplant recipient acute myeloid leukemia (AML) cells. Image adapted from Ref. (48, 49).
Figure 2
Figure 2
Natural killer (NK) cell inhibitory and activatory receptors and their ligands. Major inhibitory and activating receptors on NK cells and their cognate ligands on target cells. Image adapted from Ref. (46).
Figure 3
Figure 3
Mechanisms of the graft-versus-leukemia (GvL) effect. Host dendritic cells (DCs), activated by CD4-positive T cells, mature and can then activate CD8-positive T cells via a “license to kill” and attack leukemia cells. The leukemia cells themselves can also differentiate into self DC.
See this image and copyright information in PMC

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