Genetic Variants of the NKG2C/HLA-E Receptor-Ligand Axis Are Determinants of Progression-Free Survival and Therapy Outcome in Aggressive B-Cell Lymphoma

Cancers
Bettina WagnerVera Rebmann

Abstract

Aggressive B-cell lymphomas account for the majority of non-Hodgkin lymphomas (B-NHL). NK cells govern the responses to anti-CD20 monoclonal antibodies and have emerged as attractive targets for immunotherapy in subtypes of B-NHL. NKG2C and its cognate ligand HLA-E represent key molecules for fine-tuning of NK cell-mediated immune responses. Here, we investigated the impact of genetic variants of NKG2C and HLA-E on clinical outcomes of 441 B-NHL patients. Homozygous deletion of NKG2C (NKG2C -/- ) was three-fold increased in patients compared to 192 healthy controls. Among studied patients, NKG2C -/- was more abundant in International Prognostic Index (IPI) high-risk patients compared to patients with a lower IPI (p = 0.013). Strikingly, NKG2C -/- was associated with a significantly reduced 2-year PFS (progression-free survival) (p = 0.0062) and represented an independent risk factor for 2-year PFS in multivariate analysis (p = 0.005). For HLA-E, the cognate ligand of NKG2C, the HLA-E*01:01 allele frequency was increased in B-NHL patients compared to controls (p = 0.033) and was associated with complete remission in univariate (p = 0.034) and multivariate (p = 0.018) analysis. Our data suggest that NKG2C and HLA-E genotyping i...Continue Reading

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Methods Mentioned

BETA
genotyping

Clinical Trials Mentioned

NCT00554164

Software Mentioned

GraphPad
R package survminer
GraphPad Prism
SPSS

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