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

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-t...

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Bibliographic Details
Published in:Cancers 2020-11, Vol.12 (11), p.3429
Main Authors: Wagner, Bettina, Dührsen, Ulrich, Hüttmann, Andreas, Nückel, Holger, Michita, Rafael Tomoya, Rohn, Hana, Schramm, Sabine, Horn, Peter A., Rebmann, Vera
Format: Article
Language:English
Subjects:
Antigenic determinants
B cells
B-cell lymphoma
Care and treatment
CD20 antigen
Cell receptors
Gene deletion
Gene frequency
Genetic aspects
Genetic diversity
Genetic variation
Genotype & phenotype
Genotyping
Health aspects
Hematology
Immune response (cell-mediated)
Immune system
Immunotherapy
Ligands
Ligands (Biochemistry)
Lymphocytes B
Lymphoma
Lymphomas
Monoclonal antibodies
Multivariate analysis
Natural killer cells
NKG2 antigen
Patient outcomes
Physiological aspects
Remission
Risk factors
Risk groups
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Summary: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 is a promising tool for both defining risk groups of aggressive B-NHL and predicting response to immune therapeutic approaches.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12113429