Abstract
Human leukocyte antigen (HLA)-E is highly expressed in a variety of tumors and, in addition to immune escape, may promote tumor growth via other mechanisms. However, the role of HLA-E in neuroblastoma (NB) migration and invasion is unknown. In the present study, HLA-E expression in human NB tumors was measured by immunohistochemistry. The effect of HLA-E on NB cell migration and invasion was studied in vitro and in vivo, as well as the effect of HLA-E on natural killer (NK)-cell cytotoxicity. HLA-E was expressed in 70.2% of the NB tumor tissues examined. HLA-E expression by NB cells inhibited NK-cell cytotoxicity and induced the release of interleukin (IL)-10 and transforming growth factor (TGF)-β1. HLA-E and the released cytokines enhanced the ability of NB cells migration and invasion. NK cell infusion did not inhibit the growth of NB cells with high HLA-E expression but instead increased the number of metastatic cells in the bone marrow. Taken together, the results indicate that IL-10 and TGF-β are involved in HLA-E-mediated NB migration and invasion. Thus, HLA-E may be a new treatment target in NB.
Highlights
Neuroblastoma (NB), a high-grade malignancy with poor prognosis, originates from the primitive neural crest and is the most common extra-cranial solid tumor in children
Expression of Human leukocyte antigen (HLA)-E in NB was correlated to disease stage and N-MYC gene status
Eighty-four cases of NB were assessed for HLA-E expression
Summary
Neuroblastoma (NB), a high-grade malignancy with poor prognosis, originates from the primitive neural crest and is the most common extra-cranial solid tumor in children. More than 70% of NB patients have metastatic disease at diagnosis, which is classified as high- risk NB. Though current multidisciplinary treatment is available, the 5-year progression-free survival of highrisk NB patients is only 36%–56% [1,2]. New therapies are needed to improve treatment outcomes in NB patients. The early metastasis suggests that NB cells are highly competent. Gaining a thorough understanding of the regulatory mechanism underlying NB migration and invasion would help identify new therapeutic targets
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