Abstract
Tumor cells of classic Hodgkin lymphoma (cHL) are derived from antigen presenting B cells that are infected by Epstein Barr virus (EBV) in ~30% of patients. Polymorphic Killer cell immunoglobulin-like receptors (KIRs) expressed on NK cells interact with human leukocyte antigen (HLA) class I and play a key role in immune surveillance against virally infected cells and tumor cells. We investigated the effect of KIR types on cHL susceptibility overall (n=211) and in EBV-stratified subgroups using the Dutch GoNL cohort as controls (n=498). The frequency of the KIR haplotype B subgroup was significantly different between EBV+ and EBV− cHL patients (62% vs. 77%, p=0.04) and this difference was more pronounced in nodular sclerosis (NS) cHL (49% vs. 79%, p=0.0003). The frequency of KIR haplotype B subgroup was significantly lower in EBV+ NS cHL compared to controls (49% vs. 67%, p=0.01). Analyses of known KIR – HLA interaction pairs revealed lower carrier frequencies of KIR2DS2 – HLA-C1 (29% vs. 46%, p=0.03) and KIR2DL2 – HLA-C1 (29% vs. 45%, p=0.04) in EBV+ NS cHL patients compared to controls. Carriers of the KIR haplotype B subgroup are less likely to develop EBV+ NS cHL, probably because of a more efficient control over EBV-infected B cells.
Highlights
Hodgkin lymphoma (HL) is a B-cell derived malignancy most commonly affecting children and young adolescents
We found that Killer cell immunoglobulin-like receptors (KIRs) haplotype B subgroup protects against the development of Epstein Barr virus (EBV)+ nodular sclerosis (NS) classic Hodgkin lymphoma (cHL)
KIR2DL2 – human leukocyte antigen (HLA)-C1 and KIR2DS2 – HLA-C1 were observed at significantly lower carrier frequencies in EBV+ NS cHL patients compared to controls
Summary
Hodgkin lymphoma (HL) is a B-cell derived malignancy most commonly affecting children and young adolescents. Two main subtypes are recognized, i.e. classic HL (cHL) and nodular lymphocyte predominant HL (NLPHL), of which cHL comprises about 95% of all cases. CHL is further classified into four subtypes, i.e. nodular sclerosis (NS), mixed cellularity (MC), lymphocyte rich (LR) and lymphocyte depleted (LD). NS cHL is the most common subtype in high-income countries. KIR Susceptibility to Hodgkin Lymphoma (EBV) [2]. In these cases, monoclonal EBV genomes are present in all tumor cells suggesting that infection with EBV is an early event. EBV+ cases are observed more frequently in children, elderly, male and MC subtype patients [3,4,5]
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