Abstract
Programmed cell death 1 ligand 1(PD-L1) binds with programmed cell death protein 1 (PD-1) to inhibit the responses of T cells. PD-L1 is significantly upregulated on tumor cells and blocking the PD-L1/PD-1 signal has become an important target of immunotherapy in clinic. At present, some old drugs of non-antitumor have been found that could play the effect of anti-tumor. Maprotiline, as a tetracyclic antidepressant, has been widely used for treating mental depression. Here, we study the anti-tumor effect of maprotiline by strengthening the immune response of mice. In vitro, treatment with maprotiline inhibits the proliferation and migration of B16 cells, increases the cell apoptosis. Importantly, treatment with maprotiline reduces the expression of PD-L1 in tumor tissue, prompts the ratios of CD4+ T cells, CD8+ T cells and NK cells in spleens, increases the infiltration of CD4+ and CD8+ T cells in tumor-tissues. In brief, we determine that maprotiline could prompt the anti-tumor immune response by inhibiting the PD-L1 in mice. This study may find a new inhibitor of PD-L1, which provides a new drug treated tumor in clinical.
Nucleofection with Plasmid DNA for CRISPR/Cas9-Mediated Inactivation of Programmed Cell Death Protein 1 in CD133-Specific CAR T Cells