The Role Of Temozolomide In Modulating Immune Checkpoint Expression And Facilitating The Maturation Of Dendritic Cells

This research examines the effects of inhibitory immune checkpoint gene expression on monocyte-derived dendritic cells (moDCs) after the administration of Temozolomide (TMZ), an alkylating agent frequently used in the treatment of glioblastoma (GB). Immature monocyte-derived dendritic cells (moDCs) were induced to mature dendritic cells (mDCs) through stimulation with lipopolysaccharide (LPS). The expression of surface markers such as CD۱۱c, HLA-DR, and CD۸۶ was assessed using flow cytometry. To investigate the effect of TMZ on inhibitory immune checkpoint pathways, we measured the expression levels of PD-L۱, CTLA-۴, VISTA, BTLA, through real-time PCR in both the TMZ-treated and control mDC populations.The results of this study revealed that TMZ administration markedly enhanced the expression of maturation and antigen presentation markers, namely CD۸۶ and HLA-DR, in moDCs. Furthermore, mDCs treated with TMZ displayed a significant reduction in the expression of several inhibitory receptors, including PD-L۱, CTLA-۴, VISTA, in contrast to the control mDCs, with BTLA expression remaining consistent across both groups.These findings imply that TMZ may specifically diminish the activity of inhibitory immune checkpoints in dendritic cells that are derived from human monocytes, thereby emphasizing its prospective role in the regulation of immune responses in cancer immunotherapy

کلیدواژه ها:

Dendritic cell ، Immune Checkpoints ، Temozolomide ، Immunomodulation ، Cancer