Human leukocyte antigen-E alleles and expression in patients with serous ovarian cancer

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Abstract

Human leukocyte antigen-E (HLA-E) is one of the most extensively studied non-classical MHC class I molecules that is almost non-polymorphic. Only two alleles (HLA-E*0101 andHLA-E*0103) are found in worldwide populations, and suggested to be functional differences between these variants. The HLA-E molecule can contribute to the escape of cancer cells from host immune surveillance. However, it is still unknown whetherHLA-E gene polymorphisms might play a role in cancer immune escape. To explore the association betweenHLA-E alleles and the susceptibility to serous ovarian cancer (SOC), 85 primary SOC patients and 100 healthy women were enrolled. Here, we indicated that high frequency ofHLA-E*0103 allele existed in SOC patients by the allele-specific quantitative real-time PCR method. The levels of HLA-E protein expression in SOC patients with theHLA-E*0103 allele were higher than those with theHLA-E*0101 allele using immunohistochemistry analysis. The cell surface expression and functional differences between the two alleles were verified by K562 cells transfected withHLA-E*0101 orHLA-E*0103 allelic heavy chains. TheHLA-E*0103 allele made the transfer of the HLA-E molecule to the cell surface easier, and HLA-E/peptides complex more stable. These differences ultimately influenced the function of natural killer cells, showing that the cells transfected withHLA-E*0103 allele inhibited natural killer cells to lysis. This study reveals a novel mechanism regarding the susceptibility to SOC, which is correlated with theHLA-E*0103 allele.

In this study, we found the frequency of HLA-E*0103 allele was increased in patients with serous ovarian cancer, and HLA-E*0103/peptides complex was stable. Thus, the elevated expression of total and cell surface HLA-E molecule with HLA-E*0103 allele increased the inhibitory effect on NK cell lysis, rendering tumor cells escape from NK immune surveillance. This study is the first one to evaluate the correlation between HLA-E alleles and serous ovarian cancer.

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