» Articles » PMID: 19212329

Effects of Activating NK Cell Receptor Expression and NK Cell Reconstitution on the Outcomes of Unrelated Donor Hematopoietic Cell Transplantation for Hematologic Malignancies

Overview
Journal Leukemia
Specialties Hematology
Oncology
Date 2009 Feb 13
PMID 19212329
Citations 12
Authors
Affiliations
Soon will be listed here.
Abstract

Inhibitory NK cell receptors are recognized as important determinants of NK cell activity in hematopoietic cell transplantation (HCT). The role of activating receptors and their acquisition after HCT is less certain. Therefore, we comprehensively evaluated both inhibitory and activating receptors in 59 patients receiving unrelated donor HCT. NK cell numbers normalized quickly relative to B and T cells; however, the expression of both inhibitory and activating isoforms of killer immunoglobulin-like receptors (KIRs) was delayed. Most NK cells expressed an immature phenotype during the first 6 months post-HCT; however, we found high expression of activating NKp46 and NKp44 natural cytotoxicity receptors (NCRs), and cytotoxicity was preserved. Early reconstituting NK cells from unmanipulated grafts showed lower cytotoxicity than those from T-cell-depleted grafts. Differences in NK cell reconstitution had significant effects on clinical outcomes. Patients whose NK cells reconstituted earlier had better survival and lower relapse rates. The best survival group was recipients who possessed HLA-C2 but their donor lacked the cognate-activating KIR2DS1. Collectively, our data underscore the clinical relevance of reconstituting NK cells and their activating KIRs and NCRs. In addition to NK cell quantification and genotyping, comprehensive assessment of NK cell functions and phenotypes, including activating receptors, is essential.

Citing Articles

Investigation of KIR/HLA relationship and other clinical variables after T-cell-replete haploidentical bone marrow transplantation in patients with acute myeloid leukemia (AML).

Bakhtiari T, Ahmadvand M, Yaghmaie M, Sadeghi A, Mousavi S, Rostami T BMC Immunol. 2023; 24(1):10.

PMID: 37340345 PMC: 10283280. DOI: 10.1186/s12865-023-00548-1.


NK cells direct the perspective approaches to cancer immunotherapy.

Turki Jalil A, Abdulhadi M, Al-Marzook F, Hizam M, Abdulameer S, Al-Azzawi A Med Oncol. 2023; 40(7):206.

PMID: 37318610 DOI: 10.1007/s12032-023-02066-x.


Relevance of Polymorphic KIR and HLA Class I Genes in NK-Cell-Based Immunotherapies for Adult Leukemic Patients.

Dubreuil L, Chevallier P, Retiere C, Gagne K Cancers (Basel). 2021; 13(15).

PMID: 34359667 PMC: 8345033. DOI: 10.3390/cancers13153767.


NKp46 expression on NK cells as a prognostic and predictive biomarker for response to allo-SCT in patients with AML.

Chretien A, Devillier R, Fauriat C, Orlanducci F, Harbi S, Le Roy A Oncoimmunology. 2017; 6(12):e1307491.

PMID: 29209559 PMC: 5706596. DOI: 10.1080/2162402X.2017.1307491.


Prognostic factors and outcomes for pediatric patients receiving an haploidentical relative allogeneic transplant using CD3/CD19-depleted grafts.

Diaz M, Perez-Martinez A, Herrero B, Deltoro N, Martinez I, Ramirez M Bone Marrow Transplant. 2016; 51(9):1211-6.

PMID: 27088380 DOI: 10.1038/bmt.2016.101.


References
1.
Sivori S, Pende D, Bottino C, Marcenaro E, Pessino A, Biassoni R . NKp46 is the major triggering receptor involved in the natural cytotoxicity of fresh or cultured human NK cells. Correlation between surface density of NKp46 and natural cytotoxicity against autologous, allogeneic or xenogeneic target cells. Eur J Immunol. 1999; 29(5):1656-66. DOI: 10.1002/(SICI)1521-4141(199905)29:05<1656::AID-IMMU1656>3.0.CO;2-1. View

2.
Copelan E . Hematopoietic stem-cell transplantation. N Engl J Med. 2006; 354(17):1813-26. DOI: 10.1056/NEJMra052638. View

3.
Lowe E, Turner V, Handgretinger R, Horwitz E, Benaim E, Hale G . T-cell alloreactivity dominates natural killer cell alloreactivity in minimally T-cell-depleted HLA-non-identical paediatric bone marrow transplantation. Br J Haematol. 2003; 123(2):323-6. DOI: 10.1046/j.1365-2141.2003.04604.x. View

4.
Clausen J, Wolf D, Petzer A, Gunsilius E, Schumacher P, Kircher B . Impact of natural killer cell dose and donor killer-cell immunoglobulin-like receptor (KIR) genotype on outcome following human leucocyte antigen-identical haematopoietic stem cell transplantation. Clin Exp Immunol. 2007; 148(3):520-8. PMC: 1941931. DOI: 10.1111/j.1365-2249.2007.03360.x. View

5.
Caligiuri M . Human natural killer cells. Blood. 2008; 112(3):461-9. PMC: 2481557. DOI: 10.1182/blood-2007-09-077438. View