Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Dec 1;15(23):7330-4.
doi: 10.1158/1078-0432.CCR-09-1720. Epub 2009 Nov 24.

KIR and HLA genotypes are associated with disease progression and survival following autologous hematopoietic stem cell transplantation for high-risk neuroblastoma

Jeffrey M Venstrom  1 , Junting Zheng, Nabila Noor, Karen E Danis, Alice W Yeh, Irene Y Cheung, Bo Dupont, Richard J O'Reilly, Nai-Kong V Cheung, Katharine C Hsu
Affiliations

KIR and HLA genotypes are associated with disease progression and survival following autologous hematopoietic stem cell transplantation for high-risk neuroblastoma

Jeffrey M Venstrom et al. Clin Cancer Res. .

Abstract

Purpose: 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).

Experimental design: 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.

Conclusion: KIR-HLA immunogenetics represents a novel prognostic marker for patients undergoing autologous HSCT for high-risk neuroblastoma.

PubMed Disclaimer

Conflict of interest statement

Disclosure of Potential Conflicts of Interest

There are no relevant conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
Overall survival (A) and cumulative incidence of progression (B) following autologous HSCT in stage 4 neuroblastoma patients with all ligands present, or lacking 1 or more HLA class I ligand for inhibitory KIR.
See this image and copyright information in PMC

References

    1. Brodeur G, Maris J, editors. Neuroblastoma. 5 ed. Philadelphia: Lippincott Company; 2006.
    1. Cohn S, Pearson A, London W, Monclair T, Ambros P, Brodeur G, et al. The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol. 2009;27(2):289–297. - PMC - PubMed
    1. Simon T, Spitz R, Faldum A, Hero B, Berthold F. New definition of low-risk neuroblastoma using stage, age, and 1p and MYCN status. J Pediatr Hematol Oncol. 2004;26:791–796. - PubMed
    1. Castriconi R, Dondero A, Cilli M, Ognio E, Pezzolo A, DeGiovanni B, et al. Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice. Cancer Immunol Immunother. 2007;56:1733–1742. - PMC - PubMed
    1. Castriconi R, Dondero A, Corrias M, Lanino E, Pende D, Moretta L, et al. Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction. Cancer Res. 2004;64:9180–9184. - PubMed

Publication types