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

Rafael Tomoya Michita¹  Ulrich Dührsen²  Andreas Hüttmann²  Hana Rohn³  Vera Rebmann⁴  Sabine Schramm⁴  Bettina Wagner⁴  Peter A. Horn⁴  Holger Nückel⁵ 

[1] Department of Genetics, Institute of Biosciences, Universidade Federal do Rio Grande do Sul (UFRGS), Bento Gonçalves Avenue 9500, Campus do Vale, Porto Alegre, RS CEP 91501970, Brazil;Department of Hematology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany;Department of Infectious Diseases, West German Centre for Infectious Diseases (WZI), University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany;Institute for Transfusion Medicine, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany;Medical Practice for Hematology, Oncology, Hemostaseology and Palliative Care, 44787 Bochum, Germany;

关键词: HLA-E;    NKG2C;    NHL;    aggressive lymphoma;   

DOI  :  10.3390/cancers12113429

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown