KIR and HLA genotypes are associated with disease progression and survival following autologous hematopoietic stem cell transplantation for high-risk neuroblastoma.
OBJECTIVE
NK cells exhibit cytotoxicity against neuroblastoma. Gene polymorphisms governing NK cell function, therefore, may influence prognosis. Two highly polymorphic genetic loci instrumental in determining NK cell responses encode the NK cell killer immunoglobulin-like receptors (KIR) and their class I human leukocyte antigen (HLA) ligands. We hypothesized that patients with a "missing ligand" KIR-HLA compound genotype may uniquely benefit from autologous hematopoietic stem cell transplantation (HSCT).


METHODS
One hundred sixty-nine patients treated with autologous HSCT for stage IV neuroblastoma underwent KIR and HLA genotyping. Patients were segregated according to the presence or absence of HLA ligands for autologous inhibitory KIR. Univariate and multivariate analyses were done for overall and progression-free survival.


RESULTS
Sixty-four percent of patients lacked one or more HLA ligands for inhibitory KIR. Patients lacking a HLA ligand had a 46% lower risk of death [hazard ratio, 0.54; 95% confidence interval (95% CI), 0.35-0.85; P = 0.007] and a 34% lower risk of progression (hazard ratio, 0.66; 95% CI, 0.44-1.0; P = 0.047) at 3 years compared with patients who possessed all ligands for his/her inhibitory KIR. Among all KIR-HLA combinations, 16 patients lacking the HLA-C1 ligand for KIR2DL2/KIR2DL3 experienced the highest 3-year survival rate of 81% (95% CI, 64-100). Survival was more strongly associated with "missing ligand" than with tumor MYCN gene amplification.


CONCLUSIONS
KIR-HLA immunogenetics represents a novel prognostic marker for patients undergoing autologous HSCT for high-risk neuroblastoma.
Venstrom
Jeffrey M
JM
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Zheng
Junting
J
Noor
Nabila
N
Danis
Karen E
KE
Yeh
Alice W
AW
Cheung
Irene Y
IY
Dupont
Bo
B
O'Reilly
Richard J
RJ
Cheung
Nai-Kong V
NK
Hsu
Katharine C
KC
D000465:Algorithms; D002675:Child, Preschool; D018450:Disease Progression; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007223:Infant; D008024:Ligands; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D016017:Odds Ratio; D054340:Receptors, KIR / Q000235:genetics*; D012189:Retrospective Studies; D012306:Risk; D016896:Treatment Outcome
D006680:HLA Antigens; D008024:Ligands; D054340:Receptors, KIR