NK CELL ALLOREACTIVITY

Question 1

Introduction on NK cells and interaction with AML

Answer 1

Description of NK cells
Activating and inhibitory receptors
Interaction con with AML: ligand expression and cytotoxicity assays
Masking experiments to see the relevance of specific interactions

Question 2

HSCT in AML

Answer 2

Major treatment: conditioning regimen
Different options:
- HLA-identical bone marrow transplantation
- HLA-identical HSCT
- haploidentical HSCT: alloreactivity is expected and it may be very strong, more aggressive conditioning regimen and longer time for the engraftment

Question 3

NK cells in autologous and allogeneic context

Answer 3

Missing self recognition in both setting
Haploidentical HSCT: two situations
Graft vs leukemia effect
Advantages of alloreactive NK cells in HSCT: stronger GVL, better engraftment and prevention from GVHD > better transplantation outcome and increased tumor-free survival
T cell depletion: potential problems > leukemia relapse, rejection, toxicity of the conditioning regimen, delayed immune recovery

Question 4

NK cells in autologous and allogeneic context

Answer 4

Missing self recognition in both setting
Haploidentical HSCT: two situations
Graft vs leukemia effect
Advantages of alloreactive NK cells in HSCT: stronger GVL, better engraftment and prevention from GVHD > better transplantation outcome and increased tumor-free survival
T cell depletion: potential problems > leukemia relapse, rejection, toxicity of the conditioning regimen, delayed immune recovery

Question 5

How to choose the most suitable donor depending on NK cell alloreactivity?

Answer 5

Genetic analysis
Phenotypic analysis
Functional analysis

Redirected killing assay to distinguish between inhibitory and activating KIRs