The effect of aspartate beta-hydroxylase inhibition on immune cells

In a mouse TC-1/A9 tumor model, we found that inhibition of aspartate beta-hydroxylase (ASPH) with the small molecule inhibitor MO-I-1151 enhanced the anti-tumor effect of DNA vaccination. This combined immunotherapy also enhanced the stimulation of both CD8+ and CD4+ T cells in spleens as determined by an ELISPOT assay. To identify the target immune cells of ASPH inhibition and the mechanisms involved, we isolated splenocytes from mice treated with DNA vaccination or combined immunotherapy and CD45+ immune cells infiltrating TC-1/A9-induced tumors in control mice and mice treated with ASPH inhibition, DNA vaccination or combined immunotherapy. CellPlex was used to multiplex tumor samples and scRNA-seq was performed using the 10X Genomics platform.