Is KIR- typing relevant to HCT donor selection?

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Presentation transcript:

Is KIR- typing relevant to HCT donor selection? Dr.Taghadosi Assistant professor of immunology Kermanshah university of medical center BMT center, immunology division

NK cells NK cells are lymphoid lineage with potent cytotoxic activity against tumor cells and they show alloreactivity properties in HSCT. Less than 2% of cells in bone marrow or spleen. 5% of the lymphocytes in blood. Two major types of NK cells Stronger cytotoxic activities Weaker cytotoxic activities

NK cell target cell recognition

Killer cell activating and inhibitory receptors ©2014 American Association for Cancer Research (AACR)

KIR proteins

Killer-cell Immunoglobulin Like Receptor (KIR) genes in Leukocyte Receptor Complex (LRC) on chromosome 19

Two broad KIR haplotypes exist

KIR genes and haplotype in individuals Numerous killer‐cell immunoglobulin‐like receptor (KIR) haplotypes with different gene content have been described. A haplotypes have a single arrangement of seven expressed genes that encode mostly inhibitory KIR which are diversified by allelic variation. B haplotypes have varied gene arrangements and tend to comprise more activating genes and less allelic diversity. Genotypes that are an ‘AA’, ‘AB’ or ‘BB. Typically, a person inherits between 14 and 24 KIR genes (between 7 and 12 KIR genes per haplotype).

KIR nomenclature

18TH INTERNATIONAL HLA & IMMUNOGENETICS WORKSHOP (IHIWS) NGS: allelic typing for the HLA region and for KIR

Natural killer cell reconstitution through engraftment reconstitution Natural killer (NK) cells are the first donor-derived lymphocyte subsets to recover after hematopoietic cell transplantation . Preceding by several months the reconstitution of adaptive T and B lymphocytes. They will affects various aspect of HSCT.

Role of NK cells in various aspects of allo-HSCT Host NK cells persisting after conditioning can contribute to graft rejection. Donor NK cells can promote hematopoietic engraftment. NK cells as crucial players in preventing cancer relapse after HCT for hematologic malignancies. Controlling post transplant infection like CMV NK cells could either promote or prevent GvHD.

The concept of selecting donors by KIR genotype to optimize GVL effects after SCT for AML. A cohort of 261 patients with hematologic malignancies undergoing T-depleted myeloablative SCT. 3 donor KIR genes (2DL5A, 2DS1, and 3DS1) associated with a reduced AML relapse rate post-SCT.

KIR genotyping could be used to supplement HLA typing to improve transplant outcome for AML by allowing the selection of donors with favorable KIR types.

KIRs and their HLA class I ligands play role in the graft versus leukemia effect in AML. It seems that HLA-C1 homozygosity improves event free survival (EFS) in patients after allo-HSCT, and KIR2DS 1-positive donors are preferable for HLA-C1patients.

Effect of donor KIR genes on relapse in AML patients

NK cell contribution to graft- versus-host disease

Allogeneic bone marrow transplantation and NK cell-mediated anti-viral immunity NK cells appear to play a protective role against CMV following HSCT.