Premium
The Effects of 5‐Azacytidine on HLA‐ABC, HLA‐E, HLA‐G and HLA‐A Expression
Author(s) -
Hansen Adam,
O'Donnell Robert W.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05790
Subject(s) - human leukocyte antigen , hla g , flow cytometry , downregulation and upregulation , dna methylation , epigenetics , immunology , antigen , biology , immunotherapy , cancer research , immune system , gene expression , genetics , gene
Epigenetic modifiers, such as the DNA methylation inhibitor 5‐Azacytidine (5‐AzaC), have been shown to increase human leukocyte antigen (HLA) expression. The expression of HLA is required for a T‐cell response to detect tumor cells. A lack of HLA expression allows tumor cells to escape immune detection. It has been previously shown that 5‐AzaC is able to upregulate HLA‐ABC expression in the cell line MDA‐MB‐435. However, other HLA proteins like HLA‐E and HLA‐G may be concurrently upregulated, which would have negative implications on tumor immunity. One flask of MDA‐MB‐435 cells was treated for 48 hours with 5‐AzaC at 0.0025 mg/mL and another was left untreated. The cells were harvested and incubated with control antibodies or the experimental antibodies, Anti‐HLA‐ABC, Anti‐HLA‐G, and Anti‐HLA‐E and analyzed via flow cytometry. Preliminary experiments testing for the expression of HLA‐E and HLA‐G have both demonstrated a slight increase in their expression compared to the untreated cells. Although minor, the increase in HLA‐E and HLA‐G expression may have negative implications on tumor survival and pathogenesis. Further experimentation on HLA‐E and HLA‐G expression, as well as HLA‐A expression alone, will be conducted. Understanding individual HLA upregulation may prove to be beneficial and applicable to cancer immunotherapy, an expanding field of improved cancer treatments.